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Sample records for body giant cell

  1. Giant Cell Arteritis

    MedlinePlus

    ... Patient / Caregiver Diseases & Conditions Giant Cell Arteritis Giant Cell Arteritis Fast Facts Giant cell arteritis (GCA) is ... polymyalgia rheumatica (also called PMR). What is giant cell arteritis? GCA is a type of vasculitis or ...

  2. Macrophages, Foreign Body Giant Cells and Their Response to Implantable Biomaterials

    PubMed Central

    Sheikh, Zeeshan; Brooks, Patricia J.; Barzilay, Oriyah; Fine, Noah; Glogauer, Michael

    2015-01-01

    All biomaterials, when implanted in vivo, elicit cellular and tissue responses. These responses include the inflammatory and wound healing responses, foreign body reactions, and fibrous encapsulation of the implanted materials. Macrophages are myeloid immune cells that are tactically situated throughout the tissues, where they ingest and degrade dead cells and foreign materials in addition to orchestrating inflammatory processes. Macrophages and their fused morphologic variants, the multinucleated giant cells, which include the foreign body giant cells (FBGCs) are the dominant early responders to biomaterial implantation and remain at biomaterial-tissue interfaces for the lifetime of the device. An essential aspect of macrophage function in the body is to mediate degradation of bio-resorbable materials including bone through extracellular degradation and phagocytosis. Biomaterial surface properties play a crucial role in modulating the foreign body reaction in the first couple of weeks following implantation. The foreign body reaction may impact biocompatibility of implantation devices and may considerably impact short- and long-term success in tissue engineering and regenerative medicine, necessitating a clear understanding of the foreign body reaction to different implantation materials. The focus of this review article is on the interactions of macrophages and foreign body giant cells with biomaterial surfaces, and the physical, chemical and morphological characteristics of biomaterial surfaces that play a role in regulating the foreign body response. Events in the foreign body response include protein adsorption, adhesion of monocytes/macrophages, fusion to form FBGCs, and the consequent modification of the biomaterial surface. The effect of physico-chemical cues on macrophages is not well known and there is a complex interplay between biomaterial properties and those that result from interactions with the local environment. By having a better understanding of

  3. Foreign body giant cells selectively covering haptics of intraocular lens implants: indicators of poor toleration?

    PubMed

    Wolter, J R

    1983-10-01

    A Sputnik lens implant removed after five years because of bullous keratopathy exhibits a dense covering of its Supramid anterior staves with large foreign body giant cells, while its Prolene loops and Polymethylmethacrylate optics have attracted only few of these cell units. The glass-membrane-like component of the reactive membrane also shows significant differences on the different parts of this implant. The use of observation of the components of reactive membranes on lens implants as indicators of toleration in the eye is suggested.

  4. Fast Inactivation of Delayed Rectifier K Conductance in Squid Giant Axon and Its Cell Bodies

    PubMed Central

    Mathes, Chris; Rosenthal, Joshua J.C.; Armstrong, Clay M.; Gilly, William F.

    1997-01-01

    Inactivation of delayed rectifier K conductance (gK) was studied in squid giant axons and in the somata of giant fiber lobe (GFL) neurons. Axon measurements were made with an axial wire voltage clamp by pulsing to VK (∼−10 mV in 50–70 mM external K) for a variable time and then assaying available gK with a strong, brief test pulse. GFL cells were studied with whole-cell patch clamp using the same prepulse procedure as well as with long depolarizations. Under our experimental conditions (12–18°C, 4 mM internal MgATP) a large fraction of gK inactivates within 250 ms at −10 mV in both cell bodies and axons, although inactivation tends to be more complete in cell bodies. Inactivation in both preparations shows two kinetic components. The faster component is more temperature-sensitive and becomes very prominent above 12°C. Contribution of the fast component to inactivation shows a similar voltage dependence to that of gK, suggesting a strong coupling of this inactivation path to the open state. Omission of internal MgATP or application of internal protease reduces the amount of fast inactivation. High external K decreases the amount of rapidly inactivating IK but does not greatly alter inactivation kinetics. Neither external nor internal tetraethylammonium has a marked effect on inactivation kinetics. Squid delayed rectifier K channels in GFL cell bodies and giant axons thus share complex fast inactivation properties that do not closely resemble those associated with either C-type or N-type inactivation of cloned Kv1 channels studied in heterologous expression systems. PMID:9101403

  5. Multinucleated giant cells in the implant bed of bone substitutes are foreign body giant cells-New insights into the material-mediated healing process.

    PubMed

    Barbeck, Mike; Booms, Patrick; Unger, Ronald; Hoffmann, Verena; Sader, Robert; Kirkpatrick, Charles James; Ghanaati, Shahram

    2017-04-01

    In addition to macrophages, multinucleated giant cells (MNGCs) are involved in the tissue reaction to a variety of biomaterials. Especially in the case of bone substitute materials it has been assumed that the MNGCs are osteoclasts, based on the chemical and physical similarity of many materials to the calcified matrix and the bony environment in which they are used. However, many studies indicate that these cells belong to the cell line of the foreign body giant cells (FBGCs), which are of "inflammatory origin", although they have been shown to possess both a pro- and also anti-inflammatory phenotype. Moreover, no information is available about their role in the tissue reaction to bone substitute materials. The present study was conducted to analyze the origin of MNGCs in the implant beds of a synthetic and a xenogeneic bone substitute and focused on the application of immunohistochemical methods. Two antibodies against integrin molecules specific for osteoclasts (β-3 integrin) or FBGCs (β-2 integrin) were used to distinguish both giant cell types. The results of the present study indicate that the MNGCs induced by both kinds of bone substitutes are FBGCs, as they express only β-2 integrin in contrast to the osteoclasts outside of the immediate implantation areas, which only demonstrate β-3 integrin expression. These data give new insight into the tissue reaction to both xenogeneic and synthetic bone substitutes. Based on this new knowledge further research concerning the proteomic profile of the FBGCs especially based on the different physicochemical properties of bone substitutes is necessary. This may show that specific characteristics of bone substitutes may exhibit a substantial influence on the regeneration process via the expression of anti-inflammatory molecules by FBGCs. Based on this information it may be possible to formulate and choose bone substitutes that can guide the process of bone tissue regeneration on the molecular level. © 2017 Wiley

  6. Vitronectin is A Critical Protein Adhesion Substrate for IL-4-INDUCED Foreign Body Giant Cell Formation

    PubMed Central

    McNally, Amy K.; Jones, Jacqueline A.; MacEwan, Sarah R.; Colton, Erica; Anderson, James M.

    2014-01-01

    An in vitro system of interleukin (IL)-4-induced foreign body giant cell (FBGC) formation was utilized to define the adhesion protein substrate(s) that promotes this aspect of the foreign body reaction on biomedical polymers. Human monocytes were cultured on cell culture polystyrene surfaces that had been pre-adsorbed with a synthetic arginine-glycine-aspartate (RGD) peptide previously found to support optimal FBGC formation, or with various concentrations of potential physiological protein substrates, i.e. complement C3bi, collagen types I or IV, fibrinogen, plasma fibronectin, fibroblast fibronectin, laminin, thrombospondin, vitronectin, or von Willebrand factor. Cultures were evaluated on days 0 (1.5 hr), 3, and 7 by May-Grünwald/Giemsa staining. Initial monocyte adhesion occurred on all adsorbed proteins. However, by day 7 of culture, only vitronectin was striking in its ability to support significant macrophage adhesion, development, and fusion leading to FBGC formation. Vitronectin supported high degrees of FBGC formation at an absorption concentration between 5 and 25 μg per ml. These findings suggest that adsorbed vitronectin is critical in the collective events that support and promote FBGC formation on biomedical polymers, and that the propensity for vitronectin adsorption may underlie the material surface chemistry dependency of FBGC formation. PMID:17994558

  7. Phospholipase Cγ1 suppresses foreign body giant cell formation by maintaining RUNX1 expression in macrophages.

    PubMed

    Kim, Ye Seon; Ok, Chang Youp; Park, Joon Seong; Lee, Ha Young; Bae, Yoe-Sik

    2017-01-22

    Foreign body giant cell (FBGC) formation is associated with the inflammatory response following material implantation. However, the intracellular signaling events that regulate the process remain unclear. Here, we investigated the potential role of phospholipase C (PLC)γ1, a crucial enzyme required for growth factor-induced signaling, on FBGC formation. Knock-down of PLCγ1 using shRNA induced FBGC formation accompanied by increased expression of cathepsin K, DC-STAMP and CD36. Re-addition of PLCγ1 decreased FBGC formation. PLCγ1-deficiency caused a decrease in RUNX1 and subsequent PU.1 upregulation while subsequent rescue of RUNX1 in sh-PLCγ1-transfected cells strongly inhibited FBGC formation. FBGC generated by knock-down of PLCγ1 using shRNA resulted in strongly increased TNF-α production, with augmented activation of ERK, p38 MAPK and JNK, and subsequently NF-κB. Taken together, we suggest that PLCγ1 plays a role in the foreign body response by regulating the RUNX1/PU.1/DC-STAMP axis in macrophages. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Foreign Body Giant Cell-Related Encapsulation of a Synthetic Material Three Years After Augmentation.

    PubMed

    Lorenz, Jonas; Barbeck, Mike; Sader, Robert A; Kirkpatrick, Charles J; Russe, Philippe; Choukroun, Joseph; Ghanaati, Shahram

    2016-06-01

    Bone substitute materials of different origin and chemical compositions are frequently used in augmentation procedures to enlarge the local bone amount. However, relatively little data exist on the long-term tissue reactions. The presented case reports for the first time histological and histomorphometrical analyses of a nanocrystaline hydroxyapatite-based bone substitute material implanted in the human sinus cavity after an integration period of 3 years. The extracted biopsy was analyzed histologically and histomorphometrically with focus on the tissue reactions, vascularization, new bone formation, and the induction of a foreign body reaction. A comparably high rate of connective tissue (48.25%) surrounding the remaining bone substitute granules (42.13%) was observed. Accordingly, the amount of bone tissue (9.62%) built the smallest fraction within the biopsy. Further, tartrate-resistant acid phosphatase-positive and -negative multinucleated giant cells (4.35 and 3.93 cells/mm(2), respectively) were detected on the material-tissue interfaces. The implantation bed showed a mild vascularization of 10.03 vessels/mm(2) and 0.78%. The present case report shows that after 3 years, a comparable small amount of bone tissue was observable. Thus, the foreign body response to the bone substitute seems to be folded without further degradation or regeneration.

  9. Giant Cell Arteritis

    MedlinePlus

    Giant cell arteritis is a disorder that causes inflammation of your arteries, usually in the scalp, neck, and arms. ... arteries, which keeps blood from flowing well. Giant cell arteritis often occurs with another disorder called polymyalgia ...

  10. Chemical and physical effects on the adhesion, maturation, and survival of monocytes, macrophages, and foreign body giant cells

    NASA Astrophysics Data System (ADS)

    Collier, Terry Odell, III

    Injury caused by biomedical device implantation initiates inflammatory and wound healing responses. Cells migrate to the site of injury to degrade bacteria and toxins, create new vasculature, and form new and repair injured tissue. Blood-proteins rapidly adsorb onto the implanted material surface and express adhesive ligands which mediate cell adhesion on the material surface. Monocyte-derived macrophages and multi-nucleated foreign body giant cells adhere to the surface and degrade the surface of the material. Due to the role of macrophage and foreign body giant cell on material biocompatibility and biostability, the effects of surface chemistry, surface topography and specific proteins on the maturation and survival of monocytes, macrophages and foreign body giant cells has been investigated. Novel molecularly designed materials were used to elucidate the dynamic interactions which occur between inflammatory cells, proteins and surfaces. The effect of protein and protein adhesion was investigated using adhesive protein depleted serum conditions on RGD-modified and silane modified surfaces. The effects of surface chemistry were investigated using temperature responsive surfaces of poly (N-isopropylacrylamide) and micropatterned surfaces of N-(2 aminoethyl)-3-aminopropyltrimethoxysilane regions on an interpenetrating polymer network of polyacrylamide and poly(ethylene glycol). The physical effects were investigated using polyimide scaffold materials and polyurethane materials with surface modifying end groups. The depletion of immunoglobulin G caused decreased levels of macrophage adhesion, foreign body giant cell formation and increased levels of apoptosis. The temporal nature of macrophage adhesion was observed with changing effectiveness of adherent cell detachment with time, which correlated to increased expression of beta1 integrin receptors on detached macrophages with time. The limited ability of the micropatterned surface, polyimide scaffold and surface

  11. The Foreign Body Giant Cell Cannot Resorb Bone, But Dissolves Hydroxyapatite Like Osteoclasts

    PubMed Central

    ten Harkel, Bas; Schoenmaker, Ton; Picavet, Daisy I.; Davison, Noel L.; de Vries, Teun J.; Everts, Vincent

    2015-01-01

    Foreign body multinucleated giant cells (FBGCs) and osteoclasts share several characteristics, like a common myeloid precursor cell, multinuclearity, expression of tartrate-resistant acid phosphatase (TRAcP) and dendritic cell-specific transmembrane protein (DC-STAMP). However, there is an important difference: osteoclasts form and reside in the vicinity of bone, while FBGCs form only under pathological conditions or at the surface of foreign materials, like medical implants. Despite similarities, an important distinction between these cell types is that osteoclasts can resorb bone, but it is unknown whether FBGCs are capable of such an activity. To investigate this, we differentiated FBGCs and osteoclasts in vitro from their common CD14+ monocyte precursor cells, using different sets of cytokines. Both cell types were cultured on bovine bone slices and analyzed for typical osteoclast features, such as bone resorption, presence of actin rings, formation of a ruffled border, and characteristic gene expression over time. Additionally, both cell types were cultured on a biomimetic hydroxyapatite coating to discriminate between bone resorption and mineral dissolution independent of organic matrix proteolysis. Both cell types differentiated into multinucleated cells on bone, but FBGCs were larger and had a higher number of nuclei compared to osteoclasts. FBGCs were not able to resorb bone, yet they were able to dissolve the mineral fraction of bone at the surface. Remarkably, FBGCs also expressed actin rings, podosome belts and sealing zones—cytoskeletal organization that is considered to be osteoclast-specific. However, they did not form a ruffled border. At the gene expression level, FBGCs and osteoclasts expressed similar levels of mRNAs that are associated with the dissolution of mineral (e.g., anion exchange protein 2 (AE2), carbonic anhydrase 2 (CAII), chloride channel 7 (CIC7), and vacuolar-type H+-ATPase (v-ATPase)), in contrast the matrix degrading enzyme

  12. The Foreign Body Giant Cell Cannot Resorb Bone, But Dissolves Hydroxyapatite Like Osteoclasts.

    PubMed

    ten Harkel, Bas; Schoenmaker, Ton; Picavet, Daisy I; Davison, Noel L; de Vries, Teun J; Everts, Vincent

    2015-01-01

    Foreign body multinucleated giant cells (FBGCs) and osteoclasts share several characteristics, like a common myeloid precursor cell, multinuclearity, expression of tartrate-resistant acid phosphatase (TRAcP) and dendritic cell-specific transmembrane protein (DC-STAMP). However, there is an important difference: osteoclasts form and reside in the vicinity of bone, while FBGCs form only under pathological conditions or at the surface of foreign materials, like medical implants. Despite similarities, an important distinction between these cell types is that osteoclasts can resorb bone, but it is unknown whether FBGCs are capable of such an activity. To investigate this, we differentiated FBGCs and osteoclasts in vitro from their common CD14+ monocyte precursor cells, using different sets of cytokines. Both cell types were cultured on bovine bone slices and analyzed for typical osteoclast features, such as bone resorption, presence of actin rings, formation of a ruffled border, and characteristic gene expression over time. Additionally, both cell types were cultured on a biomimetic hydroxyapatite coating to discriminate between bone resorption and mineral dissolution independent of organic matrix proteolysis. Both cell types differentiated into multinucleated cells on bone, but FBGCs were larger and had a higher number of nuclei compared to osteoclasts. FBGCs were not able to resorb bone, yet they were able to dissolve the mineral fraction of bone at the surface. Remarkably, FBGCs also expressed actin rings, podosome belts and sealing zones--cytoskeletal organization that is considered to be osteoclast-specific. However, they did not form a ruffled border. At the gene expression level, FBGCs and osteoclasts expressed similar levels of mRNAs that are associated with the dissolution of mineral (e.g., anion exchange protein 2 (AE2), carbonic anhydrase 2 (CAII), chloride channel 7 (CIC7), and vacuolar-type H+-ATPase (v-ATPase)), in contrast the matrix degrading enzyme

  13. Tumefactive foreign body giant cell reaction following high-pressure paint injection injury: A case report and review of literature.

    PubMed

    Mauzo, Shakuntala H; Swaby, Michael G; Covinsky, Michael H

    2017-05-01

    High-pressure paint injection injury is an uncommon but well-described injury. The histologic features of long-term paint injection injury with retained material are less recognized. A 46-year-old male presented clinically as "recurrent giant cell tumor of tendon sheath." The right index finger demonstrated fusiform enlargement by a pigmented mass with diffuse infiltration into the soft tissue of the hand. Histologically the tumor showed multiple giant cells in a fibrotic stroma extending into the dermis. There were multiple types of foreign material including diffuse brown black pigment, weakly optically polarizing foreign material and white inclusions with a "train track" appearance. The cells were positive for CD68 and negative for S100 antigen. Further investigation revealed that the patient had a history of high-pressure paint injection injury to his digit 6 years prior. Foreign material injected under high pressure into tissues may result in a pseudo-neoplastic foreign body granulomatous reaction that can mimic giant cell tumor of tendon sheath. Our case demonstrates that this reaction can be florid and can have slow growth over years. A high index of suspicion, a good clinical history and careful examination can distinguish these 2 entities. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. The Giant Cell.

    ERIC Educational Resources Information Center

    Stockdale, Dennis

    1998-01-01

    Provides directions for the construction of giant plastic cells, including details for building and installing the organelles. Also contains instructions for preparing the ribosomes, nucleolus, nucleus, and mitochondria. (DDR)

  15. The Giant Cell.

    ERIC Educational Resources Information Center

    Stockdale, Dennis

    1998-01-01

    Provides directions for the construction of giant plastic cells, including details for building and installing the organelles. Also contains instructions for preparing the ribosomes, nucleolus, nucleus, and mitochondria. (DDR)

  16. Therapy-resistant foreign body giant cell granuloma at the periapex of a root-filled human tooth

    SciTech Connect

    Nair, P.N.; Sjoegren, U.K.; Krey, G.; Sundqvist, G. )

    1990-12-01

    Although the primary etiological factor of periapical lesions is microbial, there are other independent factors that can adversely affect the outcome of endodontic treatment. In this communication, we present morphological evidence in support of the role of a foreign body reaction of periapical tissue to root-filling materials. The specimen consisted of a surgical biopsy of an asymptomatic periapical lesion which persisted after a decade of postendodontic follow-up. The biopsy was processed for correlated light and electron microscopy and was analyzed by various microtechniques. The unique feature of the lesion was the presence of vast numbers of large multinucleated cells and their cytoplasmic inclusion bodies. Morphologically, these multinucleated cells resembled foreign body giant cells. They contained characteristic birefringent cytoplasmic inclusions which on electron-probe x-ray microanalysis consistently revealed the presence of magnesium and silicon. The magnesium and silicon are presumably the remnants of a root-filling excess which protruded into the periapex and had been resorbed during the follow-up period. These observations strongly suggest that in the absence of microbial factors, root-filling materials which contain irritating substances can evoke a foreign body reaction at the periapex, leading to the development of asymptomatic periapical lesions that may remain refractory to endodontic therapy for long periods of time.

  17. Therapy-resistant foreign body giant cell granuloma at the periapex of a root-filled human tooth.

    PubMed

    Nair, P N; Sjögren, U; Krey, G; Sundqvist, G

    1990-12-01

    Although the primary etiological factor of periapical lesions is microbial, there are other independent factors that can adversely affect the outcome of endodontic treatment. In this communication, we present morphological evidence in support of the role of a foreign body reaction of periapical tissue to root-filling materials. The specimen consisted of a surgical biopsy of an asymptomatic periapical lesion which persisted after a decade of postendodontic follow-up. The biopsy was processed for correlated light and electron microscopy and was analyzed by various microtechniques. The unique feature of the lesion was the presence of vast numbers of large multinucleated cells and their cytoplasmic inclusion bodies. Morphologically, these multinucleated cells resembled foreign body giant cells. They contained characteristic birefringent cytoplasmic inclusions which on electron-probe X-ray microanalysis consistently revealed the presence of magnesium and silicon. The magnesium and silicon are presumably the remnants of a root-filling excess which protruded into the periapex and had been resorbed during the follow-up period. These observations strongly suggest that in the absence of microbial factors, root-filling materials which contain irritating substances can evoke a foreign body reaction at the periapex, leading to the development of asymptomatic periapical lesions that may remain refractory to endodontic therapy for long periods of time.

  18. Giant Cell Arteritis and Polymyalgia Rheumatica

    MedlinePlus

    ... Controlfamilydoctor.org editorial staff Home Diseases and Conditions Giant Cell Arteritis and Polymyalgia Rheumatica Condition Giant Cell Arteritis and Polymyalgia Rheumatica Share Print Giant ...

  19. Regulation and Biological Significance of Formation of Osteoclasts and Foreign Body Giant Cells in an Extraskeletal Implantation Model

    PubMed Central

    Ahmed, Gazi Jased; Tatsukawa, Eri; Morishita, Kota; Shibata, Yasuaki; Suehiro, Fumio; Kamitakahara, Masanobu; Yokoi, Taishi; Koji, Takehiko; Umeda, Masahiro; Nishimura, Masahiro; Ikeda, Tohru

    2016-01-01

    The implantation of biomaterials induces a granulomatous reaction accompanied by foreign body giant cells (FBGCs). The characterization of multinucleated giant cells (MNGCs) around bone substitutes implanted in bone defects is more complicated because of healing with bone admixed with residual bone substitutes and their hybrid, and the appearance of two kinds of MNGCs, osteoclasts and FBGCs. Furthermore, the clinical significance of osteoclasts and FBGCs in the healing of implanted regions remains unclear. The aim of the present study was to characterize MNGCs around bone substitutes using an extraskeletal implantation model and evaluate the clinical significance of osteoclasts and FBGCs. Beta-tricalcium phosphate (β-TCP) granules were implanted into rat subcutaneous tissue with or without bone marrow mesenchymal cells (BMMCs), which include osteogenic progenitor cells. We also compared the biological significance of plasma and purified fibrin, which were used as binders for implants. Twelve weeks after implantation, osteogenesis was only detected in specimens implanted with BMMCs. The expression of two typical osteoclast markers, tartrate-resistant acid phosphatase (TRAP) and cathepsin-K (CTSK), was analyzed, and TRAP-positive and CTSK-positive osteoclasts were only detected beside bone. In contrast, most of the MNGCs in specimens without the implantation of BMMCs were FBGCs that were negative for TRAP, whereas the degradation of β-TCP was detected. In the region implanted with β-TCP granules with plasma, FBGCs tested positive for CTSK, and when β-TCP granules were implanted with purified fibrin, FBGCs tested negative for CTSK. These results showed that osteogenesis was essential to osteoclastogenesis, two kinds of FBGCs, CTSK-positive and CTSK-negative, were induced, and the expression of CTSK was plasma-dependent. In addition, the implantation of BMMCs was suggested to contribute to osteogenesis and the replacement of implanted β-TCP granules to bone. PMID

  20. Giant cell arteritis

    PubMed Central

    Calvo-Romero, J

    2003-01-01

    Giant cell arteritis (GCA), temporal arteritis or Horton's arteritis, is a systemic vasculitis which involves large and medium sized vessels, especially the extracranial branches of the carotid arteries, in persons usually older than 50 years. Permanent visual loss, ischaemic strokes, and thoracic and abdominal aortic aneurysms are feared complications of GCA. The treatment consists of high dose steroids. Mortality, with a correct treatment, in patients with GCA seems to be similar that of controls. PMID:13679546

  1. Giant Cell Arteritis.

    PubMed

    Hoffman, Gary S

    2016-11-01

    This issue provides a clinical overview of giant cell arteritis, focusing on diagnosis, treatment, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.

  2. What Is Giant Cell Arteritis?

    MedlinePlus

    ... 01, 2017 Giant cell arteritis (GCA) is an inflammation (swelling) of the arteries, which are the blood ... help nourish your eyes, reduced blood flow can cause sudden, painless vision loss. This condition is called ...

  3. Giant cell arteritis: a review

    PubMed Central

    Patil, Pravin; Karia, Niral; Jain, Shaifali; Dasgupta, Bhaskar

    2013-01-01

    Giant cell arteritis is the most common vasculitis in Caucasians. Acute visual loss in one or both eyes is by far the most feared and irreversible complication of giant cell arteritis. This article reviews recent guidelines on early recognition of systemic, cranial, and ophthalmic manifestations, and current management and diagnostic strategies and advances in imaging. We share our experience of the fast track pathway and imaging in associated disorders, such as large-vessel vasculitis. PMID:28539785

  4. Giant cell arteritis.

    PubMed

    Ninan, Jem; Lester, Susan; Hill, Catherine

    2016-02-01

    Giant cell arteritis (GCA) is the most common vasculitis of the elderly. The diagnosis can be challenging at times because of the limitation of the American Rheumatology Association (ARA) classification criteria and the significant proportion of biopsy-negative patients with GCA. We discuss the role of advanced imaging techniques, including positron emission tomography (PET) scanning, in establishing diagnosis and improved histopathology techniques to improve the sensitivity of temporal artery biopsy. There have been significant advances in the understanding of the pathogenesis of GCA, particularly the role of cytokine pathways such as the interleukins, IL-6-IL-17 axis, and the IL-12-interferon-γ axis and their implication for new therapies. We highlight that glucocorticoids remain the primary treatment for GCA, but recognize the risk of steroid-induced side effects. A number of pharmacotherapies to enable glucocorticoid dose reduction and prevent relapse have been studied. Early diagnosis and fast-track pathways have improved outcomes by encouraging adherence to evidence-based practice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Thiamethoxam, a poor agonist of nicotinic acetylcholine receptors expressed on isolated cell bodies, acts as a full agonist at cockroach cercal afferent/giant interneuron synapses.

    PubMed

    Thany, Steeve H

    2011-03-01

    Thiamethoxam (TMX) is a second-generation neonicotinoid which is known to induce toxic effects on insects and mammalians. Recently, it has been proposed that TMX is a poor agonist of insect nicotinic acetylcholine receptors (nAChRs) on isolated cell bodies. Here, we have studied its effect on synaptic transmission. Our results demonstrate that TMX acts as an agonist of nAChRs expressed on cockroach cercal afferent giant/interneuron synapses as bath applications of TMX induce a strong reversible depolarization of the sixth abdominal ganglion. This response was reduced by the nicotinic antagonists mecamylamine and methyllicaconitine, but was insensitive to d-tubocurarine. Interestingly, TMX-induced depolarization was partially reduced by the muscarinic antagonist atropine, suggesting that TMX could bind to a 'mixed nicotinic/muscarinic' receptor. Compared to previous studies, we proposed that TMX is able to act as agonist of insect nAChRs expressed at cercal afferent/giant interneuron synapses. Moreover, our results suggest that nAChRs expressed on synaptic ganglion are distinct to nAChRs expressed on isolated cell bodies and that synaptic receptors have higher affinity to TMX resulting to a depolarization of postsynaptic nicotinic receptors. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. Review of Giant cell arteritis

    PubMed Central

    Chacko, Joseph G.; Chacko, J. Anthony; Salter, Michael W.

    2014-01-01

    Giant-cell arteritis (GCA) is a systemic autoimmune disease affecting primarily the elderly. Giant cell arteritis can cause sudden and potentially bilateral sequential vision loss in the elderly. Therefore, it is considered a medical emergency in ophthalmology and a significant cause of morbidity in an increasingly aging population. Ophthalmologists need to be able to recognize the classic symptoms and signs of this disease, and then be able to work-up and treat these patients in an efficient manner. An in-depth review of GCA from the literature as well as personal clinical experience follows. PMID:25859139

  7. Polymyalgia Rheumatica and Giant Cell Arteritis

    MedlinePlus

    ... Clinical Trial Journal Articles Polymyalgia Rheumatica and Giant Cell Arteritis May 2016 Questions and Answers about Polymyalgia Rheumatica and Giant Cell Arteritis This publication contains general information about polymyalgia ...

  8. Giant cell tumour of the mandibular condyle.

    PubMed

    Della Sala, S W; Recla, M; Campolongo, F; Bortot, G; Bauer, M; Peterlongo, P

    1996-01-01

    The authors report a case of giant cell tumour of the mandibular condyle, which is a rare finding. This tumour, studied using the main three radiological modalities (plain radiography, CT and MRI) showed characteristic radiological features of "giant cell tumour".

  9. Observed Properties of Giant Cells

    NASA Technical Reports Server (NTRS)

    Hathaway, David H.; Upton, Lisa; Colegrove, Owen

    2014-01-01

    The existence of Giant Cells has been suggested by both theory and observation for over 45 years. We have tracked the motions of supergranules in SDO/HMI Doppler velocity data and find larger (Giant Cell) flows that persist for months. The flows in these cells are clockwise around centers of divergence in the north and counter-clockwise in the south. Equatorward flows are correlated with prograde flows - giving the transport of angular momentum toward the equator that is needed to maintain the Sun's rapid equatorial rotation. The cells are most pronounced at mid- and high-latitudes where they exhibit the rotation rates representative of those latitudes. These are clearly large, long-lived, cellular features, with the dynamical characteristics expected from the effects of the Sun's rotation, but the shapes of the cells are not well represented in numerical models. While the Giant Cell flow velocities are small (<10 m/s), their long lifetimes should nonetheless substantially impact the transport of magnetic flux in the Sun's near surface layers.

  10. Giant-cell granuloma of the axis.

    PubMed

    González-Martínez, Emilio; Santamarta, David; Lomas-García, Jesús; Ibáñez-Plágaro, F Javier; Fernández-Fernández, J Javier; Ariño, Teresa Ribas; García-Cosamalón, José

    2012-02-01

    Giant-cell granuloma is a benign and nonneoplastic lesion with an expansive and locally destructive behavior. It typically involves the mandible and the maxilla. Only 1 case arising from the odontoid process of the axis has been reported previously. The authors report on a 64-year-old man with a giant-cell granuloma of the axis. They review this uncommon entity, emphasizing the complexity of differentiating between this lesion and other giant-cell tumors.

  11. Giant cell lichenoid dermatitis in a patient with baboon syndrome.

    PubMed

    Khelifa-Hamdani, Elhem; Touati-Serraj, Monia; Perriard, Jacqueline; Chavaz, Pierre; Saurat, Jean-Hilaire; Kaya, Gürkan

    2008-10-01

    Giant cell lichenoid dermatitis is a recently described pathological entity, which can be seen as an unusual lichenoid drug eruption, a manifestation of sarcoidosis or within herpes zoster scars. Histopathological findings include focal vacuolar alteration of the basal layer with cytoid bodies, dermal and intraepidermal multinucleated giant cells and a mixed chronic inflammatory infiltrate with a lichenoid pattern consisting of lymphocytes, histiocytes, eosinophils and plasma cells. Here, we report a giant cell lichenoid dermatitis in a 41-year-old male patient who developed, 3 days after intravenous treatment with amoxicillin-clavulanic acid for erysipelas of the left leg, a clinical picture suggesting a baboon syndrome characterized by an erythematous and pruritic eruption on the axillary, inguinal and popliteal areas and the anterior side of elbows. This is the first reported case of giant cell lichenoid dermatitis in a patient with baboon syndrome.

  12. Solid-body rotation and giant circulations in coupled condensates

    NASA Astrophysics Data System (ADS)

    Mason, Peter

    2017-08-01

    This paper considers a rotating two-component condensate trapped by a harmonic plus Gaussian potential. The ability to tune the parameters to create disk-shaped or annular components, or a combination, means that different rotational regimes can appear in different components. We consider and report on these cases where there is either solid-body rotation in both components, a solid-body rotation in one component and a giant circulation in the other, or a giant circulation in both components.

  13. Phenotypic expression in human monocyte-derived interleukin-4-induced foreign body giant cells and macrophages in vitro: dependence on material surface properties.

    PubMed

    McNally, Amy K; Anderson, James M

    2015-04-01

    The effects of different material surfaces on phenotypic expression in macrophages and foreign body giant cells (FBGC) were addressed using our in vitro system of interleukin (IL)-4-induced macrophage fusion and FBGC formation. Arginine-glycine-aspartate (RGD)-, vitronectin (VN)-, and chitosan (CH)-adsorbed cell culture polystyrene, carboxylated (C, negatively charged) polystyrene, and unmodified (PS, non-cell culture treated) polystyrene were compared for their abilities to support monocyte/macrophage adhesion and IL-4-induced macrophage fusion. Pooled whole cell lysates from four different donors were evaluated by immunoblotting for expression of selected components in monocytes, macrophages, and FBGC. In addition to RGD and VN as previously shown, we find that CH supports macrophage adhesion and FBGC formation, whereas C or PS support macrophage adhesion but do not permit macrophage fusion under otherwise identical conditions of IL-4 stimulation. Likewise, components related to macrophage fusion (CD206, CD98, CD147, CD13) are strongly expressed on RGD-, VN-, and CH-adsorbed surfaces but are greatly diminished or not detected on C or PS. Importantly, material surfaces also influence the FBGC phenotype itself, as demonstrated by strong differences in patterns of expression of HLA-DR, B7-2, B7-H1, and toll-like receptor (TLR)-2 on RGD, VN, and CH despite morphologic similarities between FBGC on these surfaces. Likewise, we observe differences in the expression of B7-2, α2-macroglobulin, TLR-2, and fascin-1 between mononuclear macrophages on C and PS. Collectively, these findings reveal the extent to which material surface chemistry influences macrophage/FBGC phenotype beyond evident morphological similarities or differences and identify CH as an FBGC-supportive substrate. © 2014 Wiley Periodicals, Inc.

  14. Immunohistochemical characterization of subependymal giant cell astrocytomas.

    PubMed

    Lopes, M B; Altermatt, H J; Scheithauer, B W; Shepherd, C W; VandenBerg, S R

    1996-01-01

    Subependymal giant cell astrocytoma (SEGA) is the most common neoplastic process involving the brain in patients with tuberous sclerosis complex (TSC). Morphologically, these tumors exhibit a wide range of cytoarchitecture with spindle and epithelioid cells resembling astrocytes, and also large, occasionally giant cells, some of which have a distinctly ganglion-like appearance. Unresolved questions regarding SEGAs center on: (a) their cytogenesis, i.e., whether they are derived from single or multiple precursors; and (b) their differentiating capacity along glial or neuronal lines. We sought to determine whether SEGAs represent truly mixed tumors or whether they consist of a single population of cells with a capacity for divergent differentiation. Twenty SEGAs were assessed for immunophenotypic features of either neuronal or glial differentiation or both. Only tumors from patients with a clinically confirmed diagnosis of TSC were included. Immunoreactivity for glial fibrillary acidic protein (GFAP) and/or S-100 protein was considered indicative of a glial phenotype, whereas the presence of neuronal differentiation was assessed by staining for cytoskeletal proteins [neurofilament epitopes, class III Beta-tubulin, microtubule-associated protein 2 (MAP2), synaptophysin], neurosecretory substances [serotonin, cholecystokinin, Beta-endorphin, substance P, somatostatin, metenkephalin, neuropeptide Y, vasoactive intestinal polypeptide (VIP), and for the 28-kDa neuron-associated calcium binding protein calbindin. Of the tumors examined, 18 exhibited both glial and neuronal epitopes, the staining pattern being variable. In 19 tumors, the constituent spindle, polygonal and giant or ganglion-like cells showed variable immunoreactivity for GFAP and S-100 proteins both within the cell body and processes. Neuron-associated cytoskeletal proteins were present in 18 cases. Class III Beta-tubulin immunoreactivity was demonstrated in 17 tumors, both within the bodies of all three

  15. Synthetic hydrogel capacity to induce formation of foreign-body giant multinucleate cells differs in vivo and in vitro.

    PubMed

    Smetana, K; Holíková, Z; Seitzer, U; Haas, H; Vacík, J

    2000-01-01

    The granulomatous reaction accompanied with MGC formation represents the most striking feature of the non-favourable biological tolerance of implanted devices. We compared MGC formation in the course of the granulomatous reaction in vitro and in vivo employing three types of hydrogels whose biocompatibility had been well studied earlier. The efficiency of the in vitro assay for the granulomatous reaction, including MGC formation, was verified employing the nematode Nippostrongylus brasiliensis, a well-known inductor of MGC formation in vitro. The in vitro results demonstrated a very low level of MGC formation in reaction against all three types of hydrogels without polymer-specific differences in comparison with the nematode experiment characterized by a high extent of MGC formation. On the other hand, the extent of MGC formation was implant type-specific in vivo: pHEMA-co-DMAEMA > pHEMA > pHEMA-co-NaMA. These results indicate that in the in vitro assay it was not possible to discriminate among the types of polymers used in the experiment in comparison with the animal experiment. They also indicate potential differences between granuloma formation induced by parasites and by foreign bodies.

  16. Metaplastic ossification of the temporal artery with osteoclast-like giant cells: a mimicker of giant cell (temporal) arteritis.

    PubMed

    Sekulic, Miroslav; Truskinovsky, Alexander M

    2017-05-11

    To describe a patient presenting with suspected giant cell (temporal) arteritis (GCA) in whom subsequent temporal artery biopsy showed luminal narrowing by medial calcification, metaplastic ossification, and fibrointimal proliferation, consistent with calciphylaxis. A 55-year-old man with end-stage renal disease presented with unilateral loss of vision and elevated erythrocyte sedimentation rate and was initially treated as though he had GCA; however, a subsequent temporal artery biopsy showed marked luminal narrowing by medial calcification, metaplastic ossification, and fibrointimal proliferation, consistent with calciphylaxis. In addition, the tunica media of the affected artery contained multinucleate giant cells, but these represented osteoclasts and foreign body giant cells reacting to calcium, rather than a part of GCA. This is a rare report of metaplastic ossification and the finding of non-GCA-related giant cells in the tunica media of the temporal artery, thus representing a clinical and histopathologic mimicker of GCA. The clinical differential diagnosis of GCA includes other etiologies that can present similarly; however, temporal artery biopsy can discern the underlying pathology. Importantly, the identification of giant cells is not required for the diagnosis of GCA, and likewise, as our case shows, the finding of giant cells in the wall of a temporal artery does not always imply a diagnosis of GCA.

  17. Giant cell reparative granuloma of the axis.

    PubMed

    Bayar, Mehmet Akif; Erdem, Yavuz; Gokcek, Cevdet; Koktekir, Ender; Kilic, Celal; Yasitli, Ugur; Tekiner, Ayhan

    2009-10-01

    Giant cell reparative granuloma (GCRG) is a rare, benign fibroosseous lesion. It typically arises in the mandible and maxilla, and less frequently in the skull bones. We report a case of GCRG of the axis, which is the first to be reported in the literature. A 35-year-old man was admitted to our clinic with the complaint of pain at his neck. There was no neurological deficit. CT and MRI showed a lesion destructing the body of the axis. Biopsy specimens were taken through the transoral-transpharyngeal route. Histopathological diagnosis was GCRG. The lesion was removed subtotally by the same route. We filled the tumor cavity with a bone graft and the patient was discharged with a halo brace without any neurological deficits. The follow-up CT revealed one year after the surgery showed sclerosis at the tumor site. The etiopathogenesis of GCRG is still controversial and the differential diagnosis, especially from giant cell tumor of bone is quite difficult. The treatment of choice for these lesions is complete surgical removal. Some authors recommend radiotherapy if total removal fails.

  18. Idiopathic Giant Cell Myocarditis: A Case Report

    PubMed Central

    Kumari M.K., Kalpana; Mysorekar, Vijaya V.; S., Praveen

    2012-01-01

    Giant-cell myocarditis is a disease of relatively young, predominantly healthy adults. The patients usually die of heart failure and ventricular arrhythmia unless a cardiac transplantation is performed. We are reporting here an autopsy case of idiopathic giant cell myocarditis with no symptoms in a 27-year old -worker who died suddenly. The purpose of this report was to emphasize that idiopathic giant cell myocarditis was a rare disease and that it could exist in the absence of any symptomatic heart disease. PMID:23205365

  19. SYNOVIAL GIANT CELL TUMOR OF THE KNEE.

    PubMed

    Abdalla, Rene Jorge; Cohen, Moisés; Nóbrega, Jezimar; Forgas, Andrea

    2009-01-01

    Synovial giant cell tumor is a benign neoplasm, rarely reported in the form of malignant metastasis. Synovial giant cell tumor most frequently occurs on the hand, and, most uncommon, on the ankle and knee. In the present study, the authors describe a rare case of synovial giant cell tumor on the knee as well as the treatment approach. Arthroscopy has been shown, in this case, to be the optimal method for treating this kind of lesion, once it allowed a less aggressive approach, while providing good visualization of all compartments of knee joint and full tumor resection.

  20. SYNOVIAL GIANT CELL TUMOR OF THE KNEE

    PubMed Central

    Abdalla, Rene Jorge; Cohen, Moisés; Nóbrega, Jezimar; Forgas, Andrea

    2015-01-01

    Synovial giant cell tumor is a benign neoplasm, rarely reported in the form of malignant metastasis. Synovial giant cell tumor most frequently occurs on the hand, and, most uncommon, on the ankle and knee. In the present study, the authors describe a rare case of synovial giant cell tumor on the knee as well as the treatment approach. Arthroscopy has been shown, in this case, to be the optimal method for treating this kind of lesion, once it allowed a less aggressive approach, while providing good visualization of all compartments of knee joint and full tumor resection. PMID:27004193

  1. Giant cell arteritis presenting with uveitis.

    PubMed

    Slemp, Stephanie N; Martin, Sarah E; Burgett, Richard A; Hattab, Eyas M

    2014-10-01

    Giant cell arteritis, also known as temporal arteritis, is the most common primary vasculitis affecting the nervous system. Early recognition of this treatable condition is essential to avoid potentially devastating complications. Giant cell arteritis occurs in adults older than 50 years and affects large and medium-sized arteries, especially the external and internal carotid arteries and their branches. Severe inflammation of the vessel wall may result in obstruction of the lumen and end-organ ischemia. Typical giant cell arteritis symptoms include headache, scalp tenderness, jaw claudication, and polymyalgia rheumatica. Ischemia induced by the arteritis can lead to blindness. Herein, we describe a rare case of giant cell arteritis in a patient who initially presented with uveitis, thus eluding timely diagnosis and prompt therapy.

  2. Giant cell arteritis presenting as scalp necrosis.

    PubMed

    Maidana, Daniel E; Muñoz, Silvia; Acebes, Xènia; Llatjós, Roger; Jucglà, Anna; Alvarez, Alba

    2011-07-07

    The differential of scalp ulceration in older patients should include several causes, such as herpes zoster, irritant contact dermatitis, ulcerated skin tumors, postirradiation ulcers, microbial infections, pyoderma gangrenosum, and giant cell arteritis. Scalp necrosis associated with giant cell arteritis was first described in the 1940s. The presence of this dermatological sign within giant cell arteritis represents a severity marker of this disease, with a higher mean age at diagnosis, an elevated risk of vision loss and tongue gangrene, as well as overall higher mortality rates, in comparison to patients not presenting this manifestation. Even though scalp necrosis due to giant cell arteritis is exceptional, a high level of suspicion must be held for this clinical finding, in order to initiate prompt and proper treatment and avoid blindness.

  3. Strain difference in rats with experimental giant cell myocarditis.

    PubMed

    Shioji, K; Kishimoto, C; Nakayama, Y; Sasayama, S

    2000-04-01

    Immunogenetic mechanisms may be involved in the pathogenesis of myocarditis and dilated cardiomyopathy. The present study investigated the incidence, histopathology and histocompatibility characteristics of experimental giant cell myocarditis in various strains of rats. Experimental giant cell myocarditis was induced by immunization with porcine cardiac myosin in Lewis (RT-1(l)), Dahl (DIR/Eis) (RT-1(l)), Fisher (RT-1(lv 1)) rats, but not in Dahl (DIS/Eis) (RT-1(l)) or Brown Norway (RT-1(n)). Myocarditis was most severe in the Lewis rats and their heart weight/body weight ratio was significantly higher than that of control rats immunized with Freund's complete adjuvant alone. In conclusion, this study provides evidence that the expression and severity of experimental giant cell myocarditis may be determined mainly by genetic factors, including both major histocompatibility complex genes as well as other genes, which may be controlled by an immune mechanism.

  4. Anaplastic giant cell thyroid carcinoma.

    PubMed

    Wallin, G; Lundell, G; Tennvall, J

    2004-01-01

    Anaplastic (giant cell) thyroid carcinoma (ATC), is one of the most aggressive malignancies in humans with a median survival time after diagnosis of 3-6 months. Death from ATC was earlier seen because of local growth and suffocation. ATC is uncommon, accounting for less than 5 % of all thyroid carcinomas. The diagnosis can be established by means of multiple fine needle aspiration biopsies, which are neither harmful nor troublesome for the patient. The cytological diagnosis of this high-grade malignant tumour is usually not difficult for a well trained cytologist. The intention to treat patients with ATC is cure, although only few of them survive. The majority of the patients are older than 60 years and treatment must be influenced by their high age. We have by using a combined modality regimen succeeded in achieving local control in most patients. Every effort should be made to control the primary tumour and thereby improve the quality of remaining life and it is important for patients, relatives and the personnel to know that cure is not impossible. Different treatment combinations have been used since 30 years including radiotherapy, cytostatic drugs and surgery, when feasible. In our latest combined regimen, 22 patients were treated with hyper fractionated radiotherapy 1.6Gy x 2 to a total target dose of 46 Gy given preoperatively, 20 mg doxorubicin was administered intravenously once weekly and surgery was carried out 2-3 weeks after the radiotherapy. 17 of these 22 patients were operated upon and none of these 17 patients got a local recurrence. In the future we are awaiting the development of new therapeutic approaches to this aggressive type of carcinoma. Inhibitors of angiogenesis might be useful. Combretastatin has displayed cytotoxicity against ATC cell lines and has had a positive effect on ATC in a patient. Sodium iodide symporter (NIS) genetherapy is also being currently considered for dedifferentiated thyroid carcinomas with the ultimate aim of

  5. Sunspots and Giant-Cell Convection

    NASA Technical Reports Server (NTRS)

    Moore, Ron L.; Hathaway, David H.; Reichmann, Ed J.

    2000-01-01

    From analysis of Doppler velocity images from SOHO/MDI, Hathaway et al (2000, Solar Phys., in press) have found clear evidence for giant convection cells that fill the solar surface, have diameters 3 - 10 times that typical of supergranules, and have lifetimes approx. greater than 10 days. Analogous to the superposition of the granular convection on the supergranular convection, the approx. 30,000 km diameter supergranules are superposed on these still larger giant cells. Because the giant cells make up the large-scale end of a continuous power spectrum that peaks at the size scale of supergranules, it appears that the giant cells are made by the same mode of convection as the supergranules. This suggests that the giant cells are similar to supergranules, just longer-lived, larger in diameter, and deeper. Here we point out that the range of lengths of large bipolar sunspot groups is similar to the size range of giant cells. This, along with the long lives (weeks) of large sunspots, suggests that large sunspots sit in long-lived, deep downflows at the corners of giant cells, and that the distance from leader to follower sunspots in large bipolar groups is the distance from one giant-cell corner to the next. By this line of reasoning, an unusually large and strong downdraft might pull in both legs of a rising spot-group magnetic flux loop, resulting in the formation of a delta sunspot. This leads us to suggest that a large, strong giant-cell corner downdraft should be present at the birthplaces of large delta sunspots for some time (days to weeks) before the birth. Thus, early detection of such downdrafts by local helioscismology might provide an early warning for the formation of those active regions (large delta sunspot groups) that produce the Sun's most violent flares and coronal mass ejections. This work is supported by NASA's Office of Space Science through the Solar Physics Branch of its Sun-Earth Connection Program.

  6. Sunspots and Giant-Cell Convection

    NASA Technical Reports Server (NTRS)

    Moore, Ron L.; Hathaway, David H.; Reichmann, Ed J.

    2000-01-01

    From analysis of Doppler velocity images from SOHO/MDI, Hathaway et al (2000, Solar Phys., in press) have found clear evidence for giant convection cells that fill the solar surface, have diameters 3 - 10 times that typical of supergranules, and have lifetimes approx. greater than 10 days. Analogous to the superposition of the granular convection on the supergranular convection, the approx. 30,000 km diameter supergranules are superposed on these still larger giant cells. Because the giant cells make up the large-scale end of a continuous power spectrum that peaks at the size scale of supergranules, it appears that the giant cells are made by the same mode of convection as the supergranules. This suggests that the giant cells are similar to supergranules, just longer-lived, larger in diameter, and deeper. Here we point out that the range of lengths of large bipolar sunspot groups is similar to the size range of giant cells. This, along with the long lives (weeks) of large sunspots, suggests that large sunspots sit in long-lived, deep downflows at the corners of giant cells, and that the distance from leader to follower sunspots in large bipolar groups is the distance from one giant-cell corner to the next. By this line of reasoning, an unusually large and strong downdraft might pull in both legs of a rising spot-group magnetic flux loop, resulting in the formation of a delta sunspot. This leads us to suggest that a large, strong giant-cell corner downdraft should be present at the birthplaces of large delta sunspots for some time (days to weeks) before the birth. Thus, early detection of such downdrafts by local helioscismology might provide an early warning for the formation of those active regions (large delta sunspot groups) that produce the Sun's most violent flares and coronal mass ejections. This work is supported by NASA's Office of Space Science through the Solar Physics Branch of its Sun-Earth Connection Program.

  7. Giant cell tumor in adipose package Hoffa

    PubMed Central

    Etcheto, H. Rivarola; Escobar, G.; Blanchod, C. Collazo; Palanconi, M.; Zordan, J.; Salinas, E. Alvarez; Autorino₁, Carlos

    2017-01-01

    Tumors of adipose Hoffa package are very uncommon, with isolated cases reported in the literature. His presentation in pediatric patients knee is exceptional. The most frequently described tumors are benign including vellonodular synovitis. The extra-articular localized variant there of is known as giant cell tumor of the tendon sheath. It is characterized by locally aggressive nature, and has been described in reports of isolated cases. Objective: A case of giant cell tumor of the tendon sheath in adipose presentation package Hoffa in pediatric patients is presented in this paper. Methods: male patient eleven years with right knee pain after sports practice was evaluated. Physical examination, showed limited extension -30º, joint effusion, stable negative Lachman maneuver without peripheral knee laxity. MRI hyperintense on tumor is observed in T2 and hypointense on T1 homogeneous and defined edges content displayed prior to LCA related to adipose Hoffa package. Results: The tumor specimen was obtained and histopathology is defined as densely cellular tissue accumulation of xantomisados fibrocollagenous with histiocytes and multinucleated giant cells, compatible with giant cell tumor of tendon sheath. Conclusion: The presentation of giant cell tumors of the tendon sheath in Hoffa fat pad is exceptional. However, his suspicion allows adequate preoperative surgical planning, as a whole resection is the only procedure that has been shown to decrease the rate of recurrence of this disease.

  8. [Giant cell arteritis--case report].

    PubMed

    Napora, Katarzyna J; Obuchowska, Iwona; Mariak, Zofia

    2008-01-01

    Giant cell arteritis is a systemic disease of unknown origin. Vasculitis involves large and medium-sized vessels. Frequent clinical manifestations include characteristic headache in the temporal area, jaw or tongue claudication, apathy, fatigue, weight loss. The incidence of ocular involvement is reported in up to 70% patients. The most common and serious ophthalmic presentation is arteritic anterior ischemic optic neuropathy, which can lead to irreversible visual loss. Only early and aggressive steroid therapy may prevent this dangerous complication. The authors presented a case of a 68-years-old woman with giant cell arteritis. The main visual manifestation of this disease was anterior ischemic optic neuropathy.

  9. Immunocytochemical study of giant cell fibroma.

    PubMed

    Campos, E; Gomez, R S

    1999-01-01

    Giant cell fibroma (GCF) is a non-neoplastic lesion of the oral mucosa. The origin of stellate and multinucleate cells of GCF is not well known. The purpose of the present article was to investigate the immunoreactivity of these cells for leukocyte common antigen, vimentin, tryptase, HLA-DR, alpha-smooth muscle actin, CD68, and S-100. The results showed positive staining only for vimentin. This suggests that the stellate and multinucleate cells of GCF have a fibroblast phenotype.

  10. What Are Polymyalgia Rheumatica and Giant Cell Arteritis?

    MedlinePlus

    ... Journal Articles What Are Polymyalgia Rheumatica and Giant Cell Arteritis? PDF Version Size: 58 KB November 2014 What Are Polymyalgia Rheumatica and Giant Cell Arteritis? Fast Facts: An Easy-to-Read Series ...

  11. Expression of CD34 and CD68 in peripheral giant cell granuloma and central giant cell granuloma: An immunohistochemical analysis.

    PubMed

    Vk, Varsha; Hallikeri, Kaveri; Girish, H C; Murgod, Sanjay

    2014-01-01

    Central and Peripheral giant cell granulomas of jaws are uncommon, benign, reactive disorders that are characterized by the presence of numerous multinucleated giant cells and mononuclear cells within a stroma. The origin of the multinucleated giant cells is controversial; probably originating from fusion of histiocytes, endothelial cells and fibroblasts. To assess the expression of CD34 and CD68 in central and peripheral giant cell granulomas to understand the origin of these multinucleated giant cells. Twenty cases of Central and Peripheral giant cell granulomas were evaluated immunohistochemically for CD34 and CD68 proteins expression. Immunopositivity for CD34 was seen only in cytoplasm of endothelial cells of blood vessels; whereas, consistent cytoplasmic immunopositivity for CD68 was seen in few stromal cells. Statistical significance was seen in mean number of multinucleated giant cells, mean number of nuclei in multinucleated giant cells, CD68 expression and ratio of macrophages to multinucleated giant cells among two lesions. Although the central giant cell granulomas share some clinical and histopathological similarities with peripheral giant cell granulomas, differences in mean number of nuclei in multinucleated giant cells and CD68 immunoreactivity may underlie the distinct clinical behavior.

  12. Expression of CD34 and CD68 in peripheral giant cell granuloma and central giant cell granuloma: An immunohistochemical analysis

    PubMed Central

    VK, Varsha; Hallikeri, Kaveri; Girish, HC; Murgod, Sanjay

    2014-01-01

    Background: Central and Peripheral giant cell granulomas of jaws are uncommon, benign, reactive disorders that are characterized by the presence of numerous multinucleated giant cells and mononuclear cells within a stroma. The origin of the multinucleated giant cells is controversial; probably originating from fusion of histiocytes, endothelial cells and fibroblasts. Objective: To assess the expression of CD34 and CD68 in central and peripheral giant cell granulomas to understand the origin of these multinucleated giant cells. Materials and Methods: Twenty cases of Central and Peripheral giant cell granulomas were evaluated immunohistochemically for CD34 and CD68 proteins expression. Results: Immunopositivity for CD34 was seen only in cytoplasm of endothelial cells of blood vessels; whereas, consistent cytoplasmic immunopositivity for CD68 was seen in few stromal cells. Statistical significance was seen in mean number of multinucleated giant cells, mean number of nuclei in multinucleated giant cells, CD68 expression and ratio of macrophages to multinucleated giant cells among two lesions. Conclusion: Although the central giant cell granulomas share some clinical and histopathological similarities with peripheral giant cell granulomas, differences in mean number of nuclei in multinucleated giant cells and CD68 immunoreactivity may underlie the distinct clinical behavior. PMID:25948986

  13. Giant-cell lesions of the facial bones

    SciTech Connect

    Som, P.M.; Lawson, W.; Cohen, B.A.

    1983-04-01

    Giant-cell lesions of the paranasal sinuses, including the giant-cell reparative granuloma, the brown tumor of hyperparathyroidism, the true giant-cell tumor, cherubism, and the aneurysmal bone cyst, are uncommon entities. Plain radiographic and computed-tomographic studies of these lesions are described and the differential diagnosis is discussed.

  14. Giant-cell granuloma of the sinuses

    SciTech Connect

    Rhea, J.T.; Weber, A.L.

    1983-04-01

    Three cases are presented which illustrate giant-cell granulomas in the maxillary, ethmoid, and sphenoid sinuses. The radiographic features are nonspecific, and the lesion can mimic carcinoma. Ossification can be demonstrated, especially with computed tomography, and may indicate a benign lesion.

  15. Giant cell arteritis: diagnosis and treatment.

    PubMed

    Calvo Romero, J M

    2015-01-01

    Giant cell arteritis is the most common primary systemic vasculitis in adults. The condition is granulomatous arteritis of large and medium vessels, which occurs almost exclusively in patients aged 50 years or more. This article reviews the diagnosis and treatment of the disease. Copyright © 2015. Published by Elsevier España, S.L.U.

  16. Morphogenesis in giant-celled algae.

    PubMed

    Mine, Ichiro; Menzel, Diedrik; Okuda, Kazuo

    2008-01-01

    The giant-celled algae, which consist of cells reaching millimeters in size, some even centimeters, exhibit unique cell architecture and physiological characteristics. Their cells display a variety of morphogenetic phenomena, that is, growth, division, differentiation, and reproductive cell formation, as well as wound-healing responses. Studies using immunofluorescence microscopy and pharmacological approaches have shown that microtubules and/or actin filaments are involved in many of these events through the generation of intracellular movement of cell components or entire protoplasmic contents and the spatial control of cell activities in specific areas of the giant cells. A number of environmental factors including physical stimuli, such as light and gravity, invoke localized but also generalized cellular reactions. These have been extensively investigated to understand the regulation of morphogenesis, in particular addressing cytoskeletal and endomembrane dynamics, electrophysiological elements affecting ion fluxes, and the synthesis and mechanical properties of the cell wall. Some of the regulatory pathways involve signal transduction and hormonal control, as in other organisms. The giant unicellular green alga Acetabularia, which has proven its usefulness as an experimental model in early amputation/grafting experiments, will potentially once again serve as a useful model organism for studying the role of gene expression in orchestrating cellular morphogenesis.

  17. Sucrose-mediated giant cell formation in the genus Neisseria.

    PubMed

    Johnson, K G; McDonald, I J

    1976-03-01

    Growth of Neisseria perflava, Neisseria cinerea, and Neisseria sicca strain Kirkland in media supplemented with sucrose (0.5 to 5.0% w/v) resulted in the formation of giant cells. Response to sucrose was specific in that a variety of other carbohydrates did not mediate giant cell formation. Giant cells appeared only under growth conditions and did not lyse upon transfer to medium lacking sucrose or upon resuspension in hypotonic media. Reversion of giant to normal cells occurred when giant cells were used as inocula and allowed to multiply in media lacking sucrose.

  18. Giant Cell Tumor of Bone - An Overview

    PubMed Central

    Sobti, Anshul; Agrawal, Pranshu; Agarwala, Sanjay; Agarwal, Manish

    2016-01-01

    Giant Cell tumors (GCT) are benign tumors with potential for aggressive behavior and capacity to metastasize. Although rarely lethal, benign bone tumors may be associated with a substantial disturbance of the local bony architecture that can be particularly troublesome in peri-articular locations. Its histogenesis remains unclear. It is characterized by a proliferation of mononuclear stromal cells and the presence of many multi- nucleated giant cells with homogenous distribution. There is no widely held consensus regarding the ideal treatment method selection. There are advocates of varying surgical techniques ranging from intra-lesional curettage to wide resection. As most giant cell tumors are benign and are located near a joint in young adults, several authors favor an intralesional approach that preserves anatomy of bone in lieu of resection. Although GCT is classified as a benign lesion, few patients develop progressive lung metastases with poor outcomes. Treatment is mainly surgical. Options of chemotherapy and radiotherapy are reserved for selected cases. Recent advances in the understanding of pathogenesis are essential to develop new treatments for this locally destructive primary bone tumor. PMID:26894211

  19. Imaging of giant cell tumor of bone

    PubMed Central

    Purohit, Shaligram; Pardiwala, Dinshaw N

    2007-01-01

    Giant cell tumor (GCT) of bone is a benign but locally aggressive and destructive lesion generally occurring in skeletally mature individuals. Typically involving the epiphysiometaphyseal region of long bones, the most common sites include the distal femur, proximal tibia and distal radius. On radiographs, GCT demonstrates a lytic lesion centered in the epiphysis but involving the metaphysis and extending at least in part to the adjacent articular cortex. Most are eccentric, but become symmetric and centrally located with growth. Most cases show circumscribed borders or so-called geographical destruction with no periosteal reaction unless a pathological fracture is present. There is no mineralized tumor matrix. Giant cell tumor can produce wide-ranging appearances depending on site, complications such as hemorrhage or pathological fracture and after surgical intervention. This review demonstrates a spectrum of these features and describes the imaging characteristics of GCT in conventional radiographs, computerized tomography scans, magnetic resonance imaging, bone scans, positron emission tomography scans and angiography. PMID:21139758

  20. Giant metastatic Merkel cell carcinoma.

    PubMed

    Bognet, Rachel; Thompson, Christina; Campanelli, Carmen

    2013-01-01

    A 68-year-old man presented with a rapidly growing, asymptomatic mass on his left mid-back for the past 3 months. The patient's medical history revealed an intentional 60-pound weight loss over the previous 2 years along with smoking approximately 1 pack of cigarettes per day. On physical examination, a fungating, 11-cm red tumor with palpable broader underlying extension (23 cm total) was present on the left mid-back with distinct red dermal nodules in a dermatomal distribution. In close proximity were two ulcerated nodules, proven histologically to be basal cell carcinomas. In the left groin was massive, fixed lymphadenopathy. A punch biopsy of the tumor was performed, which showed a dense infiltrate of small, round hyperchromatic blue cells that stained positive for CD 56 and pancytokeratin in a perinuclear dot pattern. Tumor cells were negative for CK20, TTF, CK7, and LCA.

  1. Metastatic giant basal cell carcinoma: a case report

    PubMed Central

    Bellahammou, Khadija; Lakhdissi, Asmaa; Akkar, Othman; Rais, Fadoua; Naoual, Benhmidou; Elghissassi, Ibrahim; M’rabti, Hind; Errihani, Hassan

    2016-01-01

    Basal cell carcinoma is the most common skin cancer, characterised by a slow growing behavior, metastasis are extremely rare, and it occurs in less than 0, 1% of all cases. Giant basal cell carcinoma is a rare form of basal cell carcinoma, more aggressive and defined as a tumor measuring more than 5 cm at its largest diameter. Only 1% of all basal cell carcinoma develops to a giant basal cell carcinoma, resulting of patient's negligence. Giant basal cell carcinoma is associated with higher potential of metastasis and even death, compared to ordinary basal cell carcinoma. We report a case of giant basal cell carcinoma metastaticin lung occurring in a 79 years old male patient, with a fatal evolution after one course of systemic chemotherapy. Giant basal cell carcinoma is a very rare entity, early detection of these tumors could prevent metastasis occurrence and improve the prognosis of this malignancy. PMID:27795755

  2. Metastatic giant basal cell carcinoma: a case report.

    PubMed

    Bellahammou, Khadija; Lakhdissi, Asmaa; Akkar, Othman; Rais, Fadoua; Naoual, Benhmidou; Elghissassi, Ibrahim; M'rabti, Hind; Errihani, Hassan

    2016-01-01

    Basal cell carcinoma is the most common skin cancer, characterised by a slow growing behavior, metastasis are extremely rare, and it occurs in less than 0, 1% of all cases. Giant basal cell carcinoma is a rare form of basal cell carcinoma, more aggressive and defined as a tumor measuring more than 5 cm at its largest diameter. Only 1% of all basal cell carcinoma develops to a giant basal cell carcinoma, resulting of patient's negligence. Giant basal cell carcinoma is associated with higher potential of metastasis and even death, compared to ordinary basal cell carcinoma. We report a case of giant basal cell carcinoma metastaticin lung occurring in a 79 years old male patient, with a fatal evolution after one course of systemic chemotherapy. Giant basal cell carcinoma is a very rare entity, early detection of these tumors could prevent metastasis occurrence and improve the prognosis of this malignancy.

  3. Giant-Cell Arteritis and Polymyalgia Rheumatica

    PubMed Central

    Weyand, Cornelia M.; Goronzy, Jörg J.

    2014-01-01

    A 79-year-old woman presents with new-onset pain in her neck and both shoulders. She takes 7.5 mg of prednisone per day for giant-cell arteritis. Occipital tenderness and diplopia developed 11 months before presentation. At that time, her erythrocyte sedimentation rate was elevated, at 78 mm per hour, and a temporal-artery biopsy revealed granulomatous arteritis. The diplopia resolved after 6 days of treatment with 60 mg of prednisone daily. Neither headache nor visual symptoms developed when the glucocorticoids were tapered. How should this patient’s care be managed? PMID:24988557

  4. Giant many-body effects in liquid ammonia absorption spectrum

    NASA Astrophysics Data System (ADS)

    Ziaei, Vafa; Bredow, Thomas

    2016-11-01

    In the present work, we accurately calculate the absorption spectrum of liquid ammonia up to 13 eV using many-body perturbation approach. The electronic bandgap of liquid NH3 is perfectly described as the combination of density functional theory, Coulomb-hole screened exchange, and G0W0 approximation to the electronic self-energy, yielding a direct gap (Γ → Γ) of 7.71 eV, fully consistent with the experimentally measured gap from photo-emission spectroscopy. With respect to the NH3 optical properties, the entire spectrum in particular the low lying first absorption band is extremely affected by electron-hole interactions, leading to a fundamental redistribution of spectral weights of the independent-particle spectrum. Three well separated but broad main peaks are identified at 7.0, 9.8, and 11.8 eV with steadily increasing intensities in excellent agreement with the experimental data. Furthermore, we observe a giant net blue-shift of the first absorption peak of about 1.4 eV from gaseous to liquid phase as the direct consequence of many-body effects, allowing the associated liquid ammonia absorption band exciton to delocalize and feel more effectively the repulsion effects imposed by the surrounding solvent shells. Further, the spectrum is insensitive to the coupling of resonant and anti-resonant contributions. Concerning electronic response structure of liquid NH3, it is most sensitive to excitations at energies lower than its electronic gap.

  5. Giant cell (Temporal) arteritis with anterior ischemic optic neuropathy: a biopsy-proven case in Taiwan.

    PubMed

    Cheng, Cheng-Kuo; Lee, Chin-Cheng; Huang, Kai-Han; Wu, Tzu-En; Peng, Pai-Huei

    2010-07-01

    Giant cell arteritis with arteritic anterior ischemic optic neuropathy has rarely been diagnosed in Taiwan. Recently, we encountered a 76-year-old Taiwanese patient who presented with right visual impairment and marked pale swelling of his right disc. He also suffered body weight loss, general malaise and many typical manifestations of giant cell arteritis, such as jaw claudication, a tender, non-pulsating engorgement of his temporal arteries, and a highly elevated erythrocyte sedimentation rate and C-reactive protein level. Biopsy of his right superficial temporal artery revealed a granulomatous inflammation with multinucleated giant cell infiltration. This was a biopsy-proven case of giant cell arteritis with arteritic anterior ischemic optic neuropathy and indicated that although rare, this disease could occur in patients in Taiwan. Copyright 2010 Formosan Medical Association & Elsevier. Published by Elsevier B.V. All rights reserved.

  6. Peripheral giant cell granuloma: This enormity is a rarity.

    PubMed

    Rodrigues, Silvia Victor; Mitra, Dipika Kalyan; Pawar, Sudarshana Devendrasing; Vijayakar, Harshad Narayan

    2015-01-01

    Peripheral giant cell granuloma (PGCG) is an infrequent exophytic lesion of the oral cavity, also known as giant cell epulis, osteoclastoma, giant cell reparative granuloma, or giant cell hyperplasia. Lesions vary in appearance from smooth, regularly outlined masses to irregularly shaped, multilobulated protuberances with surface indentations. Ulcerations of the margin are occasionally seen. The lesions are painless, vary in size, and may cover several teeth. It normally presents as a purplish-red nodule consisting of multinucleated giant cells in the background of mononuclear stromal cells and extravasated red blood cells. This case report describes the unusual appearance of a PGCG extending from left maxillary interdental gingiva to palatal area in 32-year-old female patient.

  7. Molecular genetic analysis of giant cell glioblastomas.

    PubMed Central

    Meyer-Puttlitz, B.; Hayashi, Y.; Waha, A.; Rollbrocker, B.; Boström, J.; Wiestler, O. D.; Louis, D. N.; Reifenberger, G.; von Deimling, A.

    1997-01-01

    Glioblastomas (GBMs) are a heterogeneous group of tumors. Recently, distinct molecular genetic alterations have been linked to subgroups of patients with GBM. Giant cell (gc)GBMs are a rare variant of GBM characterized by a marked preponderance of multinucleated giant cells. Several reports have associated this entity with a more favorable prognosis than the majority of GBMs. To evaluate whether gcGBM may also represent a genetically defined subgroup of GBM, we analyzed a series of 19 gcGBMs for mutations in the TP53 gene for amplification of the EGFR and CDK4 genes and for homozygous deletions in the CDKN2A (p16/MTS1) gene. Seventeen of nineteen gcGBMs carried TP53 mutations whereas EGFR and CDK4 gene amplification was seen in only one tumor each and homozygous deletion of CDKN2A was not observed at all. The strikingly high incidence of TP53 mutations and the relative absence of other genetic alterations groups gcGBM together with a previously recognized molecular genetic variant of GBM (type 1 GBM). It is tempting to speculate that the better prognosis of gcGBM patients may result from the low incidence of EGFR amplification and CDKN2A deletion, changes known for their growth-promoting potential. Images Figure 1 PMID:9284834

  8. Usefulness of immunosuppression for giant cell myocarditis.

    PubMed

    Cooper, Leslie T; Hare, Joshua M; Tazelaar, Henry D; Edwards, William D; Starling, Randall C; Deng, Mario C; Menon, Santosh; Mullen, G Martin; Jaski, Brian; Bailey, Kent R; Cunningham, Madeleine W; Dec, G William

    2008-12-01

    Giant cell myocarditis (GCM) is a rare and highly lethal disorder. The only multicenter case series with treatment data lacked cardiac function assessments and had a retrospective design. We conducted a prospective, multicenter study of immunosuppression including cyclosporine and steroids for acute, microscopically-confirmed GCM. From June 1999 to June 2005 in a standard protocol, 11 subjects received high dose steroids and cyclosporine, and 9 subjects received muromonab-CD3. In these, 7 of 11 were women, the mean age was 60 +/- 15 years, and the mean time from symptom onset to presentation was 27 +/- 33 days. During 1 year of treatment, 1 subject died of respiratory complications on day 178, and 2 subjects received heart transplantations on days 2 and 27, respectively. Serial endomyocardial biopsies revealed that after 4 weeks of treatment the degree of necrosis, cellular inflammation, and giant cells decreased (p = 0.001). One patient who completed the trial subsequently died of a fatal GCM recurrence after withdrawal of immunosuppression. Her case demonstrates for the first time that there is a risk of recurrent, sometimes fatal, GCM after cessation of immunosuppression. In conclusion, this prospective study of immunosuppression for GCM confirms retrospective case reports that such therapy improves long-term survival. Additionally, withdrawal of immunosuppression can be associated with fatal GCM recurrence.

  9. The central giant cell granuloma in childhood: clinical case report.

    PubMed

    Loyola, Adriano Mota; Fernandes, Alexandre Vieira; Magalhaes, Aparecido Onorio; Moreira, Marilia Rodrigues

    2005-01-01

    This report reviews the literature involving the central giant cell granuloma. Diagnosis and treatment are presented. The article reports the case of central giant cell granuloma, affecting the anterior region maxillary of a child, whom a conservative treatment, with cryotherapy, helped the preservation of anterior permanent teeth germs.

  10. Natural history of giant cell tumour of the bone.

    PubMed

    Faisham, W I; Zulmi, W; Mutum, S S; Shuaib, I L

    2003-07-01

    The clinical presentation and behaviour of giant cell tumours of bone vary. The progression of the disease and metastases are unpredictable, but the overall prognosis is good. We describe the natural history and different clinical presentations of two cases of giant cell tumour of bone where the patients had refused the initial treatment and presented several years later with the disease.

  11. [Prevalence and clinicopathological characteristics of giant cell tumors].

    PubMed

    Estrada-Villaseñor, E G; Linares-González, L M; Delgado-Cedillo, E A; González-Guzmán, R; Rico-Martínez, G

    2015-01-01

    The frequency of giant cell tumors reported in the literature is very variable. Considering that our population has its own features, which distinguish it from the Anglo-Saxon and Asian populations, we think that both the frequency and the clinical characteristics of giant cell tumors in our population are different. The major aim of this paper was to determine the frequency and clinicopathological characteristics of giant cell tumors of the bone. A cross-sectional descriptive study was conducted of the cases diagnosed at our service as giant cell tumors of the bone from January to December 2013. The electronic clinical records, radiologic records and histologic slides from each case were reviewed. Giant cell tumors represented 17% of total bone tumors and 28% of benign tumors. Patients included 13 females and 18 males. The most frequent locations of giant cell tumors were: the proximal tibia, 9 cases (29%), and the distal femur, 6 cases (19%). Forty-five percent of giant cell tumors were associated with aneurysmal bone cyst (ABC) (14 cases) and one case (3%) was malignant. The frequency of giant cell tumors in this case series was intermediate, that is, higher than the one reported in Anglo-Saxon countries (usually low), but without reaching the frequency rates reported in Asian countries (high).

  12. Origin of giant cells in osteoclast-like giant cell tumors of the pancreas.

    PubMed

    Sakai, Y; Kupelioglu, A A; Yanagisawa, A; Yamaguchi, K; Hidaka, E; Matsuya, S; Ohbuchi, T; Tada, Y; Saisho, H; Kato, Y

    2000-10-01

    To clarify the origin of giant cells in osteoclast-like giant cell tumors (OGCTs) of the pancreas, we performed microscopical, immunohistochemical, and K-ras gene mutation analyses with a microdissection approach in 3 cases, featuring 4 cellular components (osteoclast-like giant cells [OGCs], pleomorphic large cells [PLCs], mononuclear cells, and ductal carcinoma cells). Two cases had abundant OGCs, and 1 case contained large number of both OGCs and PLCs. In each, none of the microdissected OGCs contained any K-ras gene mutation while they were positive for a histiocytic marker (CD-68). In contrast, PLCs, when present, frequently harbored K-ras gene mutations and were negative for CD-68. In all cases, mononuclear cells, a mixture of histiocyte-like and atypical, from microscopic and immunohistochemical viewpoints, also frequently showed K-ras alteration. Histiocyte-like mononuclear cell was equipped with a regular and oval nucleus similar to those in OGCs and was positive for CD-68. Atypical mononuclear cell showed an irregular, pleomorphic, or sometimes bizarre nucleus similar to those in PLCs and was negative for CD-68. All of the K-ras gene mutations found in PLCs and mononuclear cells were the same as in the ductal carcinoma cells within the same tumor. Thus, OGCs differ in origin from ductal cells and are strongly suggested to be nonneoplastic and of mesenchymal origin, whereas PLCs, which harbor K-ras gene mutations, are neoplastic and presumably derived from ductal carcinoma cells. Moreover, mononuclear cells may be classified into 2 types, histiocyte-like and atypical. Copyright 2000 by W.B. Saunders Company.

  13. Oral Paracoccidioidomycosis Granulomas are Predominantly Populated by CD163+ Multinucleated Giant Cells.

    PubMed

    do Prado Gomes Pedreira, Renato; de Carli, Marina Lara; Beijo, Luiz Alberto; Nonogaki, Suely; Pereira, Alessandro Antônio Costa; Junior, Noé Vital Ribeiro; Sperandio, Felipe Fornias; Hanemann, João Adolfo Costa

    2016-10-01

    Multinucleated giant cells (MGC) are considered to be a hallmark of granulomatous inflammation; thus, they may play an essential role in the host response against pathogens, particularly Paracoccidioides brasiliensis. This study characterizes the MGC found in oral paracoccidioidomycosis and assesses the correlation of MGC with the amount of fungi within oral tissues. Twenty-six cases were included. They were classified as loose or dense granulomas, and the total MGC, including foreign-body and Langhans giant cells, besides the total and intracellular fungi, were taken into consideration. CD163 immunoexpression was performed, and CD163+ multinucleated giant cells were also quantified. Dense granulomas revealed more foreign-body type and total giant cells than loose granulomas (P < 0.05). Total giant cells showed a positive linear correlation with the CD163+ cells (P = 0.003; r = 0.56) and intracellular fungi quantification (P = 0.045; r = 0.40). Oral paracoccidioidomycosis lesions contain MGC that mainly belong to a CD163+ phenotype, also showing both Langhans and foreign-body arrangements. Additionally, the higher the presence of MGC, the higher the amount of phagocytized fungi.

  14. Interleukin-1 blockade in refractory giant cell arteritis.

    PubMed

    Ly, Kim-Heang; Stirnemann, Jérôme; Liozon, Eric; Michel, Marc; Fain, Olivier; Fauchais, Anne-Laure

    2014-01-01

    Giant cell arteritis is a primary large-vessel vasculitis characterized by an arterial wall inflammation associated with intimal hyperplasia leading to arterial occlusion. Glucocorticoids remain the mainstay of giant cell arteritis treatment. However, relapses and glucocorticoid-related complications are frequent and therapeutic options for refractory giant cell arteritis are quite limited. Like tumor necrosis factor-α and interleukin-6, interleukin-1β is also highly expressed in inflamed arterial walls of patients with giant cell arteritis and may contribute in the pathogenesis of this disease. We report treatment of three cases of refractory giant cell arteritis successfully treated with anakinra, an interleukin-1 blockade therapy. Anakinra was effective for all patients, yielding improvement in their inflammation biomarkers and/or in their symptoms, as well as a disappearance of arterial inflammation in PET/CT for two of them. Copyright © 2013. Published by Elsevier SAS.

  15. Giant many-body effects in liquid ammonia absorption spectrum.

    PubMed

    Ziaei, Vafa; Bredow, Thomas

    2016-11-07

    In the present work, we accurately calculate the absorption spectrum of liquid ammonia up to 13 eV using many-body perturbation approach. The electronic bandgap of liquid NH3 is perfectly described as the combination of density functional theory, Coulomb-hole screened exchange, and G0W0 approximation to the electronic self-energy, yielding a direct gap (Γ → Γ) of 7.71 eV, fully consistent with the experimentally measured gap from photo-emission spectroscopy. With respect to the NH3 optical properties, the entire spectrum in particular the low lying first absorption band is extremely affected by electron-hole interactions, leading to a fundamental redistribution of spectral weights of the independent-particle spectrum. Three well separated but broad main peaks are identified at 7.0, 9.8, and 11.8 eV with steadily increasing intensities in excellent agreement with the experimental data. Furthermore, we observe a giant net blue-shift of the first absorption peak of about 1.4 eV from gaseous to liquid phase as the direct consequence of many-body effects, allowing the associated liquid ammonia absorption band exciton to delocalize and feel more effectively the repulsion effects imposed by the surrounding solvent shells. Further, the spectrum is insensitive to the coupling of resonant and anti-resonant contributions. Concerning electronic response structure of liquid NH3, it is most sensitive to excitations at energies lower than its electronic gap.

  16. Idiopathic giant cell myocarditis and cardiac sarcoidosis.

    PubMed

    Blauwet, Lori A; Cooper, Leslie T

    2013-11-01

    Idiopathic giant cell myocarditis (GCM) and cardiac sarcoidosis (CS) are rare disorders that cause cardiomyopathy, often with ventricular arrhythmias or heart block. Infection, autoimmune processes, and genetics have all been implicated in the pathogenesis of these diseases, but the etiology for both diseases is likely a complex multifactorial process. Both GCM and CS are generally progressive despite treatment with standard heart failure and arrhythmia therapies. Making the diagnosis of GCM or CS on initial clinical presentation is possible in only a small percentage of patients, so myocardial tissue diagnosis is required. The use of multiple noninvasive imaging modalities may aid in diagnosis and assessment of response to treatment. Establishing the diagnosis of GCM or CS early is crucial, as tailored immunosuppressive treatment may significantly alter the clinical course of these patients. The prognosis of patients with GCM is poor, while the prognosis for patients with CS varies according to degree of left ventricular dysfunction.

  17. [Intestinal infarct caused by giant cell arteritis].

    PubMed

    Kalbermatter, V; Laudanno, C; Bagilet, D; Diab, M; Giménez, D; Serra, F

    1999-01-01

    Arteritis of giant cells compromising extracranial and particularly intestinal tissues is not frequent. Therefore, it is common practice to make the diagnosis retrospectively after analyzing the surgical sample. A case is presented of an 83 year old woman admitted to the Clinical Department with a clinical course of 3 days of evolution characterized by fever and pain in the left hemiabdomen. Her personal medical history included multiple diverticulosis of colon, collecistectomy and appendicectomy. Laboratory tests showed that uremia was 0.75 g/L (N.L to 0.45 g/L), V.E.S. 90 mm at the first hour, and the rest of the determinations were normal. The chest and abdomen rays as well as the abdomen and pelvis ecographies were normal. A diagnosis was reached as acute diverticulitis and the patient was treated with 400 mgr of ciprofloxacina and 2,000 mgr a day of metronidazol. She continued in a feverish state and with abdominal pain, so that an anexial tomography of abdomen was taken. It showed a widening of peritoneal fascias with scarce liquid in the left parietocolic dripping and Douglas septum. After 96 hours, surgery exploration was done and injuries in the left colon revealed compatibility with an infarct of the colon which had to be extirpated. Pathological examination revealed an infarct of colon due to a secondary arterial thrombosis characteristic of giant cell arteritis. After the diagnosis, immunological studies and biopsy of the left temporal artery were performed and reported as normal. The patient was treated with 40 mgr of prednisone a day improving rapidly.

  18. Giant cell tumor of bone: Multimodal approach

    PubMed Central

    Gupta, AK; Nath, R; Mishra, MP

    2007-01-01

    Background: The clinical behavior and treatment of giant cell tumor of bone is still perplexing. The aim of this study is to clarify the clinico-pathological correlation of tumor and its relevance in treatment and prognosis. Materials and Methods: Ninety -three cases of giant cell tumor were treated during 1980-1990 by different methods. The age of the patients varied from 18-58 yrs with male and female ratio as 5:4. The upper end of the tibia was most commonly involved (n=31), followed by the lower end of the femur(n=21), distal end of radius(n=14), upper end of fibula (n=9), proximal end of femur(n=5), upper end of the humerus(n=3), iliac bone(n=2), phalanx (n=2) and spine(n=1). The tumors were also encountered on uncommon sites like metacarpals (n=4) and metatarsal(n=1). Fifty four cases were treated by curettage and bone grafting. Wide excision and reconstruction was performed in twenty two cases. Nine cases were treated by wide excision while primary amputation was performed in four cases. One case required only curettage. Three inaccessible lesions of ilium and spine were treated by radiotherapy. Results: 19 of 54 treated by curettage and bone grafting showed a recurrence. The repeat curettage and bone grafting was performed in 18 cases while amputation was done in one. One each out of the cases treated by wide excision and reconstruction and wide excision alone recurred. In this study we observed that though curettage and bone grafting is still the most commonly adopted treatment, wide excision of tumor with reconstruction has shown lesser recurrence. Conclusion: For radiologically well-contained and histologically typical tumor, curettage and autogenous bone grafting is the treatment of choice. The typical tumors with radiologically deficient cortex, clinically aggressive tumors and tumors with histological Grade III should be treated by wide excision and reconstruction. PMID:21139762

  19. [Anatomoclinical study of annular elastolytic giant cell granuloma].

    PubMed

    Margerin, F; Cribier, B

    2017-10-01

    Annular elastolytic giant cell granuloma (AEGCG), a rare entity first described in 1979, is very similar to O'Brien actinic granuloma (AG), first described in 1975. Since then, many cases have been published under one or other of the two names. We performed a single-centre histopathology study to identify the distinguishing features and determine whether there was any objective difference between AEGCG and AG. Cases classed as AEGCG or AG at the dermatopathology laboratory in Strasbourg were included and analysed using haematoxylin-eosin, orcein and Alcian blue staining. The diagnosis was made in the event of granuloma rich in multi-nucleated giant cells and reduction or disappearance of elastic tissue. Clinical data were collected from the analysis requests and clinical files. We identified 73 cases: 12 classed as AEGCG and 61 classed as AG. Mean age was 60.5 years with a sex ratio of 0.55. The duration of the disease ranged from 8 days to 17 years. A single lesion was seen in 52% of cases with multiple lesions in the remaining cases. Lesions measured between 0.3 and 10cm and exhibited a predilection for photo-exposed areas, chiefly on the head, neck and upper limbs. In most cases, an annular erythematous edge was seen together with a light centre, and slow centrifugal spread. The diagnosis was made by a clinician in only 5.5% of cases. These granulomas were chiefly in the superficial and mid dermis and only rarely deep, and contained numerous giant cells with a constant contingent of lymphocytes, but plasma cells were also seen in half of the cases. Orcein staining revealed marked decrease or total disappearance of elastic tissue within the granulomatous area together with elastophagocytosis in practically all images. More rarely, there was evidence of necrobiosis, palisading granuloma, vascular involvement or orcein-stained asteroid bodies. There were no notable clinical or histological differences between the cases initially classed as AEGCG or AG. AEGCG

  20. Sex, season, and time of day interact to affect body temperatures of the Giant Gartersnake

    USGS Publications Warehouse

    Wylie, G.D.; Casazza, M.L.; Halstead, B.J.; Gregory, C.J.

    2009-01-01

    1.We examined multiple hypotheses regarding differences in body temperatures of the Giant Gartersnake using temperature-sensitive radio telemetry and an information-theoretic analytical approach.2.Giant Gartersnakes selected body temperatures near 30 ??C, and males and females had similar body temperatures most of the year, except during the midsummer gestation period.3.Seasonal differences in the body temperatures of males and females may relate to both the costs associated with thermoregulatory behavior, such as predation, and the benefits associated with maintaining optimal body temperatures, such as successful incubation.

  1. Annular elastolytic giant cell granuloma in association with Hashimoto's thyroiditis

    PubMed Central

    Hassan, Rishi; Arunprasath, P.; Padmavathy, L.; Srivenkateswaran, K.

    2016-01-01

    Annular elastolytic giant cell granuloma (AEGCG) is a rare granulomatous skin disease characterized clinically by annular plaques with elevated borders and atrophic centers found mainly on sun-exposed skin and histologically by diffuse granulomatous infiltrates composed of multinucleated giant cells, histiocytes and lymphocytes in the dermis along with phagocytosis of elastic fibers by multinucleated giant cells. We report a case of AEGCG in a 50-year-old woman and is highlighted for the classical clinical and histological findings of the disease and its rare co-existence with Hashimoto's thyroiditis. PMID:27057492

  2. Subependymal giant cell astrocytoma: diagnosis, screening, and treatment. Recommendations from the International Tuberous Sclerosis Complex Consensus Conference 2012.

    PubMed

    Roth, Jonathan; Roach, E Steve; Bartels, Ute; Jóźwiak, Sergiusz; Koenig, Mary Kay; Weiner, Howard L; Franz, David N; Wang, Henry Z

    2013-12-01

    Tuberous sclerosis complex is an autosomal dominant disorder predisposing to the development of benign lesions in different body organs, mainly in the brain, kidney, liver, skin, heart, and lung. Subependymal giant cell astrocytomas are characteristic brain tumors that occur in 10% to 20% of tuberous sclerosis complex patients and are almost exclusively related to tuberous sclerosis complex. Subependymal giant cell astrocytomas usually grow slowly, but their progression ultimately leads to the occlusion of the foramen of Monro, with subsequent increased intracranial pressure and hydrocephalus, thus necessitating intervention. During recent years, secondary to improved understanding in the biological and genetic basis of tuberous sclerosis complex, mammalian target of rapamycin inhibitors have been shown to be effective in the treatment of subependymal giant cell astrocytomas, becoming an alternative therapeutic option to surgery. In June 2012, an International Tuberous Sclerosis Complex Consensus Conference was convened, during which an expert panel revised the diagnostic criteria and considered treatment options for subependymal giant cell astrocytomas. This article summarizes the subpanel's recommendations regarding subependymal giant cell astrocytomas. Mammalian target of rapamycin inhibitors have been shown to be an effective treatment of various aspects of tuberous sclerosis complex, including subependymal giant cell astrocytomas. Both mammalian target of rapamycin inhibitors and surgery have a role in the treatment of subependymal giant cell astrocytomas. Various subependymal giant cell astrocytoma-related conditions favor a certain treatment. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Reactive Nitrogen Intermediates in Giant Cell Arteritis

    PubMed Central

    Borkowski, Astrid; Younge, Brian R.; Szweda, Luke; Mock, Bettina; Björnsson, Johannes; Moeller, Kerstin; Goronzy, Jörg J.; Weyand, Cornelia M.

    2002-01-01

    Arterial wall damage in giant cell arteritis (GCA) is mediated by several different macrophage effector functions, including the production of metalloproteinases and lipid peroxidation. Tissue-invading macrophages also express nitric oxide synthase (NOS)-2, but it is not known whether nitric oxide-related mechanisms contribute to the disease process. Nitric oxide can form nitrating agents, including peroxynitrite, a nitric oxide congener formed in the presence of reactive oxygen intermediates. Protein nitration selectively targets tyrosine residues and can result in a gain, as well as a loss, of protein function. Nitrated tyrosine residues in GCA arteries were detected almost exclusively on endothelial cells of newly formed microcapillaries in the media, whereas microvessels in the adventitia and the intima were spared. Nitration correlated with endothelial NOS-3 expression and not with NOS-2-producing macrophages, which preferentially homed to the hyperplastic intima. The restriction of nitration to the media coincided with the production of reactive oxygen intermediates as demonstrated by the presence of the toxic aldehyde, 4-hydroxynonenal. Depletion of tissue-infiltrating macrophages in human temporal artery-SCID mouse chimeras disrupted nitrotyrosine generation, demonstrating a critical role of macrophages in the nitration process that targeted medial microvessels. Thus, protein nitration in GCA is highly compartmentalized, reflecting the production of reactive oxygen and reactive nitrogen intermediates in the inflamed arterial wall. Heterogeneity of microvessels in NOS-3 regulation may be an additional determinant contributing to this compartmentalization and could explain the preferential targeting of newly generated capillary beds. PMID:12107096

  4. Giant Cell Arteritis - Beyond temporal artery biopsy and steroids.

    PubMed

    Ninan, Jem V; Lester, Susan; Hill, Catherine L

    2017-05-09

    Giant cell arteritis is the commonest primary vasculitis of the elderly. The acute complications of untreated Giant cell arteritis such as vision loss or occasionally stroke can be devastating. The diagnosis is however not altogether straightforward due to variable sensitivities of the temporal artery biopsy as a reference diagnostic test. In this review, we discuss the increasing role of imaging in the diagnosis of Giant cell arteritis. Glucocorticoid treatment is the backbone of therapy but it is associated with significant adverse effects. A less toxic alternative is required. Conventional and novel immunosuppressive agents have only demonstrated modest effects in a subgroup of steroid refractory Giant cell arteritis due to the different arms of the immune system at play. However, recently a study of IL-6 blockade demonstrated benefit in GCA. The current status of these immunosuppressive agents and novel therapies are also discussed in this review. This article is protected by copyright. All rights reserved.

  5. Paroxysmal hemicrania as the clinical presentation of giant cell arteritis.

    PubMed

    Beams, Jennifer L; Rozen, Todd D

    2011-09-28

    Head pain is the most common complaint in patients with giant cell arteritis but the headache has no distinct diagnostic features. There have been no published reports of giant cell arteritis presenting as a trigeminal autonomic cephalalgia. We describe a patient who developed a new onset headache in her fifties, which fit the diagnostic criteria for paroxysmal hemicrania and was completely responsive to corticosteroids. Removal of the steroid therapy brought a reemergence of her headaches. Giant cell arteritis should be considered in the evaluation of secondary causes of paroxysmal hemicrania; in addition giant cell arteritis needs to be ruled out in patients who are over the age of 50 years with a new onset trigeminal autonomic cephalalgia.

  6. Paroxysmal hemicrania as the clinical presentation of giant cell arteritis

    PubMed Central

    Beams, Jennifer L.; Rozen, Todd D.

    2011-01-01

    Head pain is the most common complaint in patients with giant cell arteritis but the headache has no distinct diagnostic features. There have been no published reports of giant cell arteritis presenting as a trigeminal autonomic cephalalgia. We describe a patient who developed a new onset headache in her fifties, which fit the diagnostic criteria for paroxysmal hemicrania and was completely responsive to corticosteroids. Removal of the steroid therapy brought a reemergence of her headaches. Giant cell arteritis should be considered in the evaluation of secondary causes of paroxysmal hemicrania; in addition giant cell arteritis needs to be ruled out in patients who are over the age of 50 years with a new onset trigeminal autonomic cephalalgia. PMID:24765352

  7. Giant cell tumor of soft tissue arising in breast.

    PubMed

    May, Steve A; Deavers, Michael T; Resetkova, Erika; Johnson, Deborah; Albarracin, Constance T

    2007-10-01

    Primary giant cell tumor of soft tissue (GCT-ST) arising in breast is exceedingly rare. We report a case of a 60-year-old woman with a primary breast giant cell tumor that appeared histologically identical to giant cell tumor of bone and had a clinically malignant course. The patient presented with a cystic mass of the breast, suspected on imaging to be an organizing hematoma, possibly related to previous injury. Histopathological evaluation revealed a neoplasm composed of mononuclear cells admixed with osteoclast-like giant cells resembling giant cell tumor of bone. Immunohistochemical staining was positive for CD68, smooth muscle actin, and vimentin, but was negative for a panel of epithelial and additional muscle markers. These features were most consistent with GCT-ST, an uncommon neoplasm of low malignant potential. Despite aggressive surgical treatment achieving clear surgical margins, the patient expired with pulmonary metastases within a year of her initial presentation. This case demonstrates the difficulty of predicting clinical behavior of GCT-ST of breast on the basis of histological features and depth of tumor alone. To our knowledge, this is the first case report of a GCT-ST arising in the breast associated with a fatal outcome. The distinction of this entity from other more common primary breast tumors with giant cell morphology is also emphasized.

  8. [Trochanteric bursitis, pelvic enthesopathy and giant cell arteritis].

    PubMed

    Lorléac'h, A; Duffau, P; Michaux, C; Greib, C; Caubet, O; Viallard, J-F; Pellegrin, J-L

    2008-12-01

    Giant cell arteritis, a large-sized vessel vasculitis, may be associated with musculoskeletal proximal (polymyalgia rheumatica) or distal manifestations. A 68-year-old woman, who had inflammatory pelvic girdle pain, was diagnosed with giant cell arteritis and was successfully treated with corticosteroids. The magnetic resonance imaging and ultrasonography revealed a bilateral bursitis and pelvic girdle enthesopathy. Bursitis is the main anatomic lesion occurring in polymyalgia rheumatica and can be underlined by ultrasonography.

  9. Annular elastolytic giant cell granuloma: A report of 10 cases

    PubMed Central

    Arora, Sandeep; Malik, Ajay; Patil, Chetan; Balki, Anil

    2015-01-01

    Annular elastolytic giant cell granuloma initially described by O’Brien in 1975 is a disorder of uncertain etiopathogenesis presenting with annular erythematous plaques predominantly on the sun-exposed areas. Hisptopathologically, it is characterized by elastin degenration, multinucleate giant cells, and elastophagocytosis. The authors came across 10 such cases, which were managed with hydroxychloroquine resulting in complete resolution in 4–6 months. PMID:26904442

  10. Giant cell reparative granuloma presenting as a midline nasal mass.

    PubMed

    Govett, G S; Amedee, R G

    1991-03-01

    Giant cell reparative granuloma (GCRG) is an uncommon entity that has been reported in all areas of the head and neck. It must be distinguished from true giant cell tumors, brown tumors of hyperparathyroidism, aneurysmal bone cysts, and fibrous dysplasia. It responds well to surgical debulking and curettage and has a benign clinical course. We describe a case report of a GCRG presenting as a midline nasal mass and review the pertinent English language literature.

  11. Recurrent Giant Cell Tumor of Skull Combined with Multiple Aneurysms

    PubMed Central

    Kim, Dae Hwan

    2016-01-01

    Giant cell tumors are benign but locally invasive and frequently recur. Giant cell tumors of the skull are extremely rare. A patient underwent a surgery to remove a tumor, but the tumor recurred. Additionally, the patient developed multiple aneurysms. The patient underwent total tumor resection and trapping for the aneurysms, followed by radiotherapy. We report this rare case and suggest some possibilities for treating tumor growth combined with aneurysm development. PMID:27195256

  12. Giant cells in anaplastic mammary carcinoma of the dog and cat.

    PubMed

    Della Salda, L; Sarli, G; Benazzi, C; Marcato, P S

    1993-11-01

    Four uncommon anaplastic mammary carcinomas containing numerous giant cells are described in three dogs and one cat. The giant cells of all cases were studied by means of monoclonal and polyclonal antibodies to detect epithelial (carcinoembryonic antigen and keratin) and mesenchymal (vimentin, lysozyme and S-100 protein) differentiation. Most of them proved to have an epithelial immunophenotype. Ultrastructurally, scattered bundles of tonofilaments but no lysosome-like bodies could be detected. One tumour had an additional, different type of giant cell, which had a benign multinucleated osteoclast-like appearance, gave positive staining for acid phosphatase, had a histiocytic-stromal immunohistochemical pattern, and was, ultrastructurally, multinucleate with irregular folds and no evidence of tonofilaments. In one case some giant cells had an epithelial immunophenotype and others a stromal immunophenotype, even though their histological and ultrastructural features were the same. In the least histologically differentiated tumour the giant cells presented a coexpression of intermediate filaments. This supported the theory that there might be a stem cell origin for most canine mammary tumours.

  13. HHV-6A in syncytial giant-cell hepatitis.

    PubMed

    Potenza, Leonardo; Luppi, Mario; Barozzi, Patrizia; Rossi, Giulio; Cocchi, Stefania; Codeluppi, Mauro; Pecorari, Monica; Masetti, Michele; Di Benedetto, Fabrizio; Gennari, William; Portolani, Marinella; Gerunda, Giorgio Enrico; Lazzarotto, Tiziana; Landini, Maria Paola; Schulz, Thomas F; Torelli, Giuseppe; Guaraldi, Giovanni

    2008-08-07

    Syncytial giant-cell hepatitis is a rare but severe form of hepatitis that is associated with autoimmune diseases, drug reactions, and viral infections. We used serologic, molecular, and immunohistochemical methods to search for an infectious cause in a case of syncytial giant-cell hepatitis that developed in a liver-transplant recipient who had latent infection with variant B of human herpesvirus 6 (HHV-6B) and who had received the organ from a donor with variant A latent infection (HHV-6A). At the onset of the disease, the detection of HHV-6A (but not HHV-6B) DNA in plasma, in affected liver tissue, and in single micromanipulated syncytial giant cells with the use of two different polymerase-chain-reaction (PCR) assays indicated the presence of active HHV-6A infection in the patient. Expression of the HHV-6A-specific early protein, p41/38, but not of the HHV-6B-specific late protein, p101, was demonstrated only in liver syncytial giant cells in the absence of other infectious pathogens. The same markers of HHV-6A active infection were documented in serial follow-up samples from the patient and disappeared only at the resolution of syncytial giant-cell hepatitis. Neither HHV-6B DNA nor late protein was identified in the same follow-up samples from the patient. Thus, HHV-6A may be a cause of syncytial giant-cell hepatitis.

  14. Genetic Alterations in Gliosarcoma and Giant Cell Glioblastoma.

    PubMed

    Oh, Ji Eun; Ohta, Takashi; Nonoguchi, Naosuke; Satomi, Kaishi; Capper, David; Pierscianek, Daniela; Sure, Ulrich; Vital, Anne; Paulus, Werner; Mittelbronn, Michel; Antonelli, Manila; Kleihues, Paul; Giangaspero, Felice; Ohgaki, Hiroko

    2016-07-01

    The majority of glioblastomas develop rapidly with a short clinical history (primary glioblastoma IDH wild-type), whereas secondary glioblastomas progress from diffuse astrocytoma or anaplastic astrocytoma. IDH mutations are the genetic hallmark of secondary glioblastomas. Gliosarcomas and giant cell glioblastomas are rare histological glioblastoma variants, which usually develop rapidly. We determined the genetic patterns of 36 gliosarcomas and 19 giant cell glioblastomas. IDH1 and IDH2 mutations were absent in all 36 gliosarcomas and in 18 of 19 giant cell glioblastomas analyzed, indicating that they are histological variants of primary glioblastoma. Furthermore, LOH 10q (88%) and TERT promoter mutations (83%) were frequent in gliosarcomas. Copy number profiling using the 450k methylome array in 5 gliosarcomas revealed CDKN2A homozygous deletion (3 cases), trisomy chromosome 7 (2 cases), and monosomy chromosome 10 (2 cases). Giant cell glioblastomas had LOH 10q in 50% and LOH 19q in 42% of cases. ATRX loss was detected immunohistochemically in 19% of giant cell glioblastomas, but absent in 17 gliosarcomas. These and previous results suggest that gliosarcomas are a variant of, and genetically similar to, primary glioblastomas, except for a lack of EGFR amplification, while giant cell glioblastoma occupies a hybrid position between primary and secondary glioblastomas. © 2015 International Society of Neuropathology.

  15. New developments in giant cell arteritis.

    PubMed

    Frohman, Larry; Wong, Aaron B C; Matheos, Kaliopy; Leon-Alvarado, Luis G; Danesh-Meyer, Helen V

    2016-01-01

    Giant cell arteritis (GCA) is a medium-to-large vessel vasculitis with potentially sight- and life- threatening complications. Our understanding of the pathogenesis, diagnosis, and treatment of GCA has advanced rapidly in recent times. The validity of using the American College of Rheumatology guidelines for diagnosis of GCA in a clinical setting has been robustly challenged. Erythrocyte sedimentation rate, an important marker of inflammation, is lowered by the use of statins and nonsteroidal anti-inflammatory drugs. Conversely, it may be falsely elevated with a low hematocrit. Despite the emergence of new diagnostic modalities, temporal artery biopsy remains the gold standard. Evidence suggests that shorter biopsy lengths and biopsies done weeks to months after initiation of steroid therapy are still useful. New imaging techniques such as positron emission tomography have shown that vascular inflammation in GCA is more widespread than originally thought. GCA, Takayasu arteritis, and polymyalgia rheumatica are no longer thought to exist as distinct entities and are more likely parts of a spectrum of disease. A range of immunosuppressive drugs have been used in conjunction with corticosteroids to treat GCA. In particular, interleukin-6 inhibitors are showing promise as a therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Arthroplasty for tenosynovial giant cell tumors

    PubMed Central

    Verspoor, Floortje G M; Hannink, Gerjon; Scholte, Anouk; Van Der Geest, Ingrid C M; Schreuder, H W Bart

    2016-01-01

    Background and purpose Tenosynovial giant cell tumors (t-GCTs) can behave aggressively locally and affect joint function and quality of life. The role of arthroplasty in the treatment of t-GCT is uncertain. We report the results of arthroplasty in t-GCT patients. Patients and methods t-GCT patients (12 knee, 5 hip) received an arthroplasty between 1985 and 2015. Indication for arthroplasty, recurrences, complications, quality of life, and functional scores were evaluated after a mean follow-up time of 5.5 (0.2–15) years. Results 2 patients had recurrent disease. 2 other patients had implant loosening. Functional scores showed poor results in almost half of the knee patients. 4 of the hip patients scored excellent and 1 scored fair. Quality of life was reduced in 1 or more subscales for 2 hip patients and for 5 knee patients. Interpretation In t-GCT patients with extensive disease or osteoarthritis, joint arthroplasty is an additional treatment option. However, recurrences, implant loosening, and other complications do occur, even after several years. PMID:27357329

  17. Giant cell arteritis among Hispanic Americans.

    PubMed

    Lam, Byron L; Wirthlin, Robert S; Gonzalez, Ariadna; Dubovy, Sander R; Feuer, William J

    2007-01-01

    To compare the prevalence and clinical course of giant cell arteritis (GCA) among Hispanic and non-Hispanic patients. Comparative case series. Two hundred fifty-seven consecutive patients who underwent temporal artery biopsy in our institution from 1996 to 2002 were studied. A prospective telephone survey was conducted to determine race and Hispanic origin separately by means of methodology of the US Census Bureau. One hundred thirty-four patients completed the interview, with 65 (49%) identifying themselves as Hispanic and 69 (51%) as non-Hispanic. Of the 32 respondents with biopsy-proven GCA, all identified themselves racially as white, and 13 (41%) were Hispanic and 19 (59%) were non-Hispanic (P = .32). Statistically significant differences in age, presenting symptoms, and final visual acuity were not observed among Hispanic and non-Hispanic patients with GCA. Although GCA has been reported to be rare in Hispanics, we found the prevalence and clinical course of GCA to be similar in Hispanic and non-Hispanic patients.

  18. Giant cell tumor of the spine.

    PubMed

    Ozaki, Toshifumi; Liljenqvist, Ulf; Halm, Henry; Hillmann, Axel; Gosheger, Georg; Winkelmann, Winfried

    2002-08-01

    Six patients with giant cell tumor of the spine had surgery between 1981 and 1995. Three lesions were located in the scrum, two lesions were in the thoracic spine, and one lesion was in the lumbar spine. Preoperatively, all patients had local pain and neurologic symptoms. Two patients had cement implanted after curettage or intralesional excision of the sacral tumor; one patient had a local relapse. After the second curettage and cement implantation, the tumor was controlled. One patient with a sacral lesion had marginal excision and spondylodesis; no relapse developed. Two patients with thoracic lesions had planned marginal excision and spondylodesis; the margins finally became intralesional, but no relapse developed. One patient with a lumbar lesion had incomplete removal of the tumor and received postoperative irradiation. At the final followup (median, 69 months), five of six patients were disease-free and one patient died of disease progression. Two of the five surviving patients had pain after standing or neurologic problems. Although some contamination occurred, planning a marginal excision of the lesion seems beneficial for vertebral lesions above the sacrum. Total sacrectomy of a sacral lesion seems to be too invasive when cement implantation can control the lesion.

  19. Giant cell arteritis: Current treatment and management

    PubMed Central

    Ponte, Cristina; Rodrigues, Ana Filipa; O’Neill, Lorraine; Luqmani, Raashid Ahmed

    2015-01-01

    Glucocorticoids remain the cornerstone of medical therapy in giant cell arteritis (GCA) and should be started immediately to prevent severe consequences of the disease, such as blindness. However, glucocorticoid therapy leads to significant toxicity in over 80% of the patients. Various steroid-sparing agents have been tried, but robust scientific evidence of their efficacy and safety is still lacking. Tocilizumab, a monoclonal IL-6 receptor blocker, has shown promising results in a number of case series and is now being tested in a multi-centre randomized controlled trial. Other targeted treatments, such as the use of abatacept, are also now under investigation in GCA. The need for surgical treatment is rare and should ideally be performed in a quiescent phase of the disease. Not all patients follow the same course, but there are no valid biomarkers to assess therapy response. Monitoring of disease progress still relies on assessing clinical features and measuring inflammatory markers (C-reactive protein and erythrocyte sedimentation rate). Imaging techniques (e.g., ultrasound) are clearly important screening tools for aortic aneurysms and assessing patients with large-vessel involvement, but may also have an important role as biomarkers of disease activity over time or in response to therapy. Although GCA is the most common form of primary vasculitis, the optimal strategies for treatment and monitoring remain uncertain. PMID:26090367

  20. Giant cell tumors of the axial skeleton.

    PubMed

    Balke, Maurice; Henrichs, Marcel P; Gosheger, Georg; Ahrens, Helmut; Streitbuerger, Arne; Koehler, Michael; Bullmann, Viola; Hardes, Jendrik

    2012-01-01

    Background. We report on 19 cases of giant cell tumor of bone (GCT) affecting the spine or sacrum and evaluate the outcome of different treatment modalities. Methods. Nineteen patients with GCT of the spine (n = 6) or sacrum (n = 13) have been included in this study. The mean followup was 51.6 months. Ten sacral GCT were treated by intralesional procedures of which 4 also received embolization, and 3 with irradiation only. All spinal GCT were surgically treated. Results. Two (15.4%) patients with sacral and 4 (66.7%) with spinal tumors had a local recurrence, two of the letter developed pulmonary metastases. One local recurrence of the spine was successfully treated by serial arterial embolization, a procedure previously described only for sacral tumors. At last followup, 9 patients had no evidence of disease, 8 had stable disease, 1 had progressive disease, 1 died due to disease. Six patients had neurological deficits. Conclusions. GCT of the axial skeleton have a high local recurrence rate. Neurological deficits are common. En-bloc spondylectomy combined with embolization is the treatment of choice. In case of inoperability, serial arterial embolization seems to be an alternative not only for sacral but also for spinal tumors.

  1. Giant Cell Tumors of the Axial Skeleton

    PubMed Central

    Balke, Maurice; Henrichs, Marcel P.; Gosheger, Georg; Ahrens, Helmut; Streitbuerger, Arne; Koehler, Michael; Bullmann, Viola; Hardes, Jendrik

    2012-01-01

    Background. We report on 19 cases of giant cell tumor of bone (GCT) affecting the spine or sacrum and evaluate the outcome of different treatment modalities. Methods. Nineteen patients with GCT of the spine (n = 6) or sacrum (n = 13) have been included in this study. The mean followup was 51.6 months. Ten sacral GCT were treated by intralesional procedures of which 4 also received embolization, and 3 with irradiation only. All spinal GCT were surgically treated. Results. Two (15.4%) patients with sacral and 4 (66.7%) with spinal tumors had a local recurrence, two of the letter developed pulmonary metastases. One local recurrence of the spine was successfully treated by serial arterial embolization, a procedure previously described only for sacral tumors. At last followup, 9 patients had no evidence of disease, 8 had stable disease, 1 had progressive disease, 1 died due to disease. Six patients had neurological deficits. Conclusions. GCT of the axial skeleton have a high local recurrence rate. Neurological deficits are common. En-bloc spondylectomy combined with embolization is the treatment of choice. In case of inoperability, serial arterial embolization seems to be an alternative not only for sacral but also for spinal tumors. PMID:22448122

  2. Extracranial giant cell arteritis: A narrative review.

    PubMed

    Lensen, K D F; Voskuyl, A E; Comans, E F I; van der Laken, C J; Smulders, Y M

    2016-06-01

    A systematic literature search was performed to summarise current knowledge on extracranial giant cell arteritis (GCA), i.e. large-artery involvement in patients with or without clinically apparent temporal arteritis (cranial GCA). Extracranial GCA is increasingly recognised, both in patients with cranial GCA and with solitary extracranial GCA, due to increased awareness among physicians and development of modern imaging modalities. The literature on the pathogenesis and histopathology of extracranial GCA is scarce. It is considered to be similar to cranial GCA. Patients with solitary extracranial GCA often present with non-specific signs and symptoms, although vascular manifestations, mostly secondary to stenosis, may occur. Due to the non-specific clinical presentation and low sensitivity of temporal artery biopsies, extracranial GCA is usually diagnosed by imaging. 18F-FDG-PET, MRI, CT angiography and ultrasound are used for this purpose. At present, the optimal diagnostic strategy is undetermined. The choice for a particular modality can be guided by the clinical scenario that raises suspicion of extracranial GCA, in addition to local availability and expertise. Extracranial complications in GCA consist of aortic aneurysm or dissection (mainly the ascending aorta), aortic arch syndrome, arm claudication and posterior stroke (although this is technically a cranial complication, it often results from stenosis of the vertebrobasilar arteries). Mortality is generally not increased in patients with GCA. Treatment of patients with solitary extracranial and those with extracranial and cranial GCA has been debated in the recent literature. In general, the same strategy is applied as in patients with temporal arteritis, although criteria regarding who to treat are unclear. Surgical procedures may be indicated, in which case optimal medical treatment prior to surgery is important.

  3. Rare Giant Cell Tumor of Olecranon Bone!!!!

    PubMed Central

    Goyal, Pawan; Gautam, Vishal; Saini, Narender; Sharma, Yogesh

    2016-01-01

    Introduction: Giant cell tumor (GCT) is a bone tumor involving epiphyseal area of bone abutting the subchondral bone. Commonly found in long bones such as proximal tibia and distal femur. We report a case of GCT of olecranon bone in a 23-year-old male. Case Report: A 23-year-old patient presented to our outpatient department with pain and mild swelling at the elbow from last 2 to 3 months. On examination, it was seen that there was a moderate swelling at the tip of the olecranon. The magnetic resonance imaging reported a lytic lesion in the olecranon but sparing the coronoid process of the ulna, the biopsy report confirmed that histologically it was a GCT of the bone. Total excision of the tumor was done after lifting the aponeurosis of the triceps muscle. The area remaining after excision of the tumor was phenol cauterized and cleaned with hydrogen peroxide solution. Triceps was reinserted on the remaining ulna. At follow-up the radiographs showed adequate excision of the tumor. The patient gained a full range of movement at the elbow and was functionally restored. There were no signs of any systemic spread of the tumor. Conclusion: GCT though a very common bone tumor could be missed if present in atypical locations. Radiographically soap bubble appearance might not be present in every case, and there could be multiple diagnoses for lytic lesion in bone. Proper investigations and histopathological examination are necessary for accurate diagnosis and further treatment planning. Early treatment helps in complete excision of tumor along with return of adequate function of the patient. PMID:28164048

  4. A Search for Giant Convection Cells on the Sun

    NASA Technical Reports Server (NTRS)

    Hathaway, David H.

    1998-01-01

    Giant convection cells (slow, long-lived cellular flows in the Sun's convection zone with typical diameters greater than about 100,000 km) have been the subject of many searches over the last 30 years. If such flows exist, they should play a key role in structuring the Sun's large scale magnetic field and in driving the large scale axisymmetric flows: the differential rotation and meridional circulation. Detailed observations of the flows in these cells may also allow us to better predict future magnetic field configurations and the solar activity associated with them. Line-of-sight velocity data from the Michelson Doppler Interferometer on the ESA/NASA Solar and Heliospheric Observatory provides us with new opportunities to search for giant cells. This data is free of any atmospheric distortion and has been obtained continuously without any day/night gaps for more than two months at a time. These two-month datasets are important because giant cells are expected to have lifetimes somewhat longer that the Sun's 27 day rotation period. Any reappearance of a flow pattern after 27 days would be an important confirmation of the existence of these cells. The approach taken in this search is to separate the giant cell velocity signal from the other, stronger velocity signals by using a spherical harmonic representation of the spatial structures and a fourier decomposition of the temporal behavior. Any giant cell signal should be characterized by low spatial wavenumbers with temporal frequencies appropriate to the solar rotation of these patterns.

  5. [Giant cell tumor of the C2 colonized by an aneurismal bone cyst. Report of case].

    PubMed

    Cebula, H; Boujan, F; Beaujeux, R; Boyer, P; Froelich, S

    2012-12-01

    Giant cell tumor is colonized by aneurismal bone cyst in only 15% of cases and cervical localisation accounts for less than 1% of giant cell tumors. We are reporting a rare case of a C2 hypervascularized giant cell tumor colonized by an aneurismal bone cyst treated with an effective preoperative Onyx embolization followed by a full tumor resection. The patient experienced a moderate cervical spine injury 2 months prior admission followed by a progressive stiff neck and cervicalgia. CT and MRI identified a lytic lesion of the body and lateral masses of the C2 with encasement of both vertebral arteries. The angiography showed a hypervascularization of the lesion from the vertebral and external carotid arteries as well as a thrombosis of the V3 segment of the right vertebral artery at the C1 level. A posterior occipito-C3/C4 fixation and a tumor biopsy were performed. Histopathological examination concluded to a giant cell tumor colonized by an aneurismal bone cyst. Three weeks later, the patient developed a right upper extremity deficit. The MRI showed an increased C1-C2 stenosis and an increase of the hypervascularization. Three sessions of embolization by the onyx were performed. During surgery a near total tumor devascularisation was observed and a complete resection of the tumor was achieved through an anterolateral approach. Reconstruction consisted of a cementoplasty of the C2 body and odontoïd process with an anterior C3-prosthesis plate. The postoperative course was uneventful.

  6. Multifocal Central Giant Cell Granuloma - A Case Report

    PubMed Central

    Sandhya, Tamgadge; Avinash, Tamgadge; Snehal, Dhauskar; Neha, Tiwari; Uma, Mudaliar

    2016-01-01

    Central giant cell granuloma is a benign, aggressive neoplasm composed of multinucleated giant cells that almost exclusively occurs in the jaws though extra- gnathic incidence is rare. Multifocal CGCGs of the jaws are very rare and suggestive of systemic diseases such as hyperparathyroidism, an inherited syndrome such as Noonan- like multiple giant cell lesion syndrome or other disorders.Very few cases of multifocal CGCGs in the jaws without any concomitant systemic disease have been reported. This paper describes an unusual case reported to the Oral Surgery Department of Dr. D.Y.Patil Dental College & Hospital, Nerul, Navi-Mumbai in 2014 in a 45-year-old male with multifocal central giant cell granuloma involving maxilla and mandible. The serum alkaline phosphatase, calcium and phosphorus levels were within the normal limits. After complete clinical examination hyperparathyroidism and clinical characteristic of any syndromes such as Noonan-like syndrome and neurofibromatosis were ruled out. Thus this paper reports a non-syndromic multifocal central giant cell granuloma. PMID:27799978

  7. Peripheral Giant Cell Granuloma: A Review of 123 Cases

    PubMed Central

    Shadman, Niloofar; Ebrahimi, Shahram Farzin; Jafari, Shahin; Eslami, Mohammad

    2009-01-01

    Background: Peripheral giant cell granuloma is one of the reactive hyperplastic lesions of the oral cavity, which originates from the periosteum or periodontal membrane following local irritation or chronic trauma. The purpose of this study was to present the clinical characteristics of peripheral giant cell granuloma in a group of Iranian population. Methods: A series of 123 consecutive confirmed cases of peripheral giant cell granuloma after biopsy were evaluated. Age, sex, anatomic location, consistency, etiologic factor, pain and bleeding history, color, surface texture, and pedicle situation were recorded and were analyzed by chi-square test and values were considered to be significant if P < 0.05. Results: Age ranged from 6 to 75 years (mean 33 years). Women affected more than men (M/F 1:1.1). Peripheral giant cell granuloma was seen in the mandible more than in the maxilla and in the anterior region more than in the posterior region. In most cases, lesions were pink, pedunculated and had non-ulcerated surface. In less than half of the cases, there was no history of bleeding and also pain was rarely reported. Calculus was the most common etiologic factor. Conclusion: The results confirmed that the clinical features of peripheral giant cell granuloma in a group of Iranian population are almost similar to those reported by other investigators. PMID:21528029

  8. Idiopathic giant cell myocarditis in childhood: A case report.

    PubMed

    Pehlivan, Sultan; Akçan, Ramazan; Heybet, Eyup Ruşen; Cavlak, Mehmet; Pehlivan, Ali

    2016-03-01

    Idiopathic giant cell myocarditis is a rare entity of unknown origin, which causes sudden death in more than half of the affected patients. It is rarely seen in childhood, and might result in death due to heart failure and ventricular arrhythmias. Idiopathic giant cell myocarditis is mostly diagnosed at autopsy incidentally. Here we present a rare case of childhood idiopathic giant cell myocarditis. A 10-year old boy found dead in his bed in the morning. Interview with family members revealed death the boy was in good health conditions apart from being overweight. At autopsy, external examination was completely normal. Internal examination revealed normal findings; the heart was 297g and macroscopically normal. No traces of any toxic agents detected in complete toxicological analyses. Areas characterized with granulomatous lesions, lymphocytes, histiocytes, and multinucleated giant cells were observed in myocardium at histopathological examination. No necrosis was observed in granulomatous areas. Tuberculosis was negative in the PCR assays. There were no signs indicative of fungal infection, and clinical status of the case was not compatible with the sarcoidosis. In this respect death was attributed to idiopathic giant cell myocarditis.

  9. Timescales of Quartz Crystallization and the Longevity of the Bishop Giant Magma Body

    SciTech Connect

    Gualda, Guilherme A.R.; Pamukcu, Ayla S.; Ghiorso, Mark S.; Anderson, Jr. , Alfred T.; Sutton, Stephen R.; Rivers, Mark L.

    2013-04-08

    Supereruptions violently transfer huge amounts (100 s-1000 s km{sup 3}) of magma to the surface in a matter of days and testify to the existence of giant pools of magma at depth. The longevity of these giant magma bodies is of significant scientific and societal interest. Radiometric data on whole rocks, glasses, feldspar and zircon crystals have been used to suggest that the Bishop Tuff giant magma body, which erupted {approx}760,000 years ago and created the Long Valley caldera (California), was long-lived (>100,000 years) and evolved rather slowly. In this work, we present four lines of evidence to constrain the timescales of crystallization of the Bishop magma body: (1) quartz residence times based on diffusional relaxation of Ti profiles, (2) quartz residence times based on the kinetics of faceting of melt inclusions, (3) quartz and feldspar crystallization times derived using quartz+feldspar crystal size distributions, and (4) timescales of cooling and crystallization based on thermodynamic and heat flow modeling. All of our estimates suggest quartz crystallization on timescales of <10,000 years, more typically within 500-3,000 years before eruption. We conclude that large-volume, crystal-poor magma bodies are ephemeral features that, once established, evolve on millennial timescales. We also suggest that zircon crystals, rather than recording the timescales of crystallization of a large pool of crystal-poor magma, record the extended periods of time necessary for maturation of the crust and establishment of these giant magma bodies.

  10. Timescales of quartz crystallization and the longevity of the Bishop giant magma body.

    PubMed

    Gualda, Guilherme A R; Pamukcu, Ayla S; Ghiorso, Mark S; Anderson, Alfred T; Sutton, Stephen R; Rivers, Mark L

    2012-01-01

    Supereruptions violently transfer huge amounts (100 s-1000 s km(3)) of magma to the surface in a matter of days and testify to the existence of giant pools of magma at depth. The longevity of these giant magma bodies is of significant scientific and societal interest. Radiometric data on whole rocks, glasses, feldspar and zircon crystals have been used to suggest that the Bishop Tuff giant magma body, which erupted ~760,000 years ago and created the Long Valley caldera (California), was long-lived (>100,000 years) and evolved rather slowly. In this work, we present four lines of evidence to constrain the timescales of crystallization of the Bishop magma body: (1) quartz residence times based on diffusional relaxation of Ti profiles, (2) quartz residence times based on the kinetics of faceting of melt inclusions, (3) quartz and feldspar crystallization times derived using quartz+feldspar crystal size distributions, and (4) timescales of cooling and crystallization based on thermodynamic and heat flow modeling. All of our estimates suggest quartz crystallization on timescales of <10,000 years, more typically within 500-3,000 years before eruption. We conclude that large-volume, crystal-poor magma bodies are ephemeral features that, once established, evolve on millennial timescales. We also suggest that zircon crystals, rather than recording the timescales of crystallization of a large pool of crystal-poor magma, record the extended periods of time necessary for maturation of the crust and establishment of these giant magma bodies.

  11. Cell-to-cell transfer of glial proteins to the squid giant axon: The glia- neuron protein transfer hypothesis

    PubMed Central

    Lasek, RJ; Gainer, H; Barker, JL

    1977-01-01

    The hypothesis that glial cells synthesize proteins which are transferred to adjacent neurons was evaluated in the giant fiber of the squid (Loligo pealei). When giant fibers are separated from their neuron cell bodies and incubated in the presence of radioactive amino acids, labeled proteins appear in the glial cells and axoplasm. Labeled axonal proteins were detected by three methods: extrusion of the axoplasm from the giant fiber, autoradiography, and perfusion of the giant fiber. This protein synthesis is completely inhibited by puromycin but is not affected by chloramphenicol. The following evidence indicates that the labeled axonal proteins are not synthesized within the axon itself. (a) The axon does not contain a significant amount of ribosomes or ribosomal RNA. (b) Isolated axoplasm did not incorporate [(3)H]leucine into proteins. (c) Injection of Rnase into the giant axon did not reduce the appearance of newly synthesized proteins in the axoplasm of the giant fiber. These findings, coupled with other evidence, have led us to conclude that the adaxonal glial cells synthesize a class of proteins which are transferred to the giant axon. Analysis of the kinetics of this phenomenon indicates that some proteins are transferred to the axon within minutes of their synthesis in the glial cells. One or more of the steps in the transfer process appear to involve Ca++, since replacement of extracellular Ca++ by either Mg++ or Co++ significantly reduces the appearance of labeled proteins in the axon. A substantial fraction of newly synthesized glial proteins, possibly as much as 40 percent, are transferred to the giant axon. These proteins are heterogeneous and range in size from 12,000 to greater than 200,000 daltons. Comparisons of the amount of amino acid incorporation in glia cells and neuron cell bodies raise the possibility that the adaxonal glial cells may provide an important source of axonal proteins which is supplemental to that provided by axonal transport

  12. Giant-cell arteritis without cranial manifestations

    PubMed Central

    de Boysson, Hubert; Lambert, Marc; Liozon, Eric; Boutemy, Jonathan; Maigné, Gwénola; Ollivier, Yann; Ly, Kim; Manrique, Alain; Bienvenu, Boris; Aouba, Achille

    2016-01-01

    Abstract Diagnosis of giant-cell arteritis (GCA) is challenging in the absence of cardinal cranial symptoms/signs. We aimed to describe the clinical presentation, diagnostic process, and disease course of GCA patients without cranial symptoms, and to compare them to those of patients with typical cranial presentation. In this retrospective multicenter study, we enrolled patients with GCA who satisfied at least 3 of the 5 American College of Rheumatology criteria for GCA, or 2 criteria associated with contributory vascular biopsy other than temporal artery biopsy or with demonstration of large-vessel involvement; underwent iconographic evaluation of large arterial vessels (aortic CT scan or a positron emission tomography with 18F-fluorodeoxyglucose combined with computed tomography (FDG-PET/CT) scan or cardiac echography combined with a large-vessel Doppler) at diagnosis. We divided the cohort into 2 groups, distinguishing between patients without cranial symptoms/signs (i.e., headaches, clinical temporal artery anomaly, jaw claudication, ophthalmologic symptoms) and those with cranial symptoms/signs. In the entire cohort of 143 patients, all of whom underwent vascular biopsy and vascular imaging, we detected 31 (22%) patients with no cranial symptoms/signs. In the latter, diagnosis was biopsy proven in an arterial sample in 23 cases (74% of patients, on a temporal site in 20 cases and on an extratemporal site in 3). One-third of these 31 patients displayed extracranial symptoms/signs whereas the remaining two-thirds presented only with constitutional symptoms and/or inflammatory laboratory test results. Compared to the 112 patients with cardinal cranial clinical symptoms/signs, patients without cranial manifestations displayed lower levels of inflammatory laboratory parameters (C-reactive level: 68 [9–250] mg/L vs 120 [3–120] mg/L; P < 0.01), highest rate of aorta and aortic branch involvement identified (19/31 (61%) vs 42/112 (38%); P = 0.02) and also

  13. Relapses in Patients With Giant Cell Arteritis

    PubMed Central

    Alba, Marco A.; García-Martínez, Ana; Prieto-González, Sergio; Tavera-Bahillo, Itziar; Corbera-Bellalta, Marc; Planas-Rigol, Ester; Espígol-Frigolé, Georgina; Butjosa, Montserrat; Hernández-Rodríguez, José; Cid, Maria C.

    2014-01-01

    Abstract Giant cell arteritis (GCA) is a relapsing disease. However, the nature, chronology, therapeutic impact, and clinical consequences of relapses have been scarcely addressed. We conducted the present study to investigate the prevalence, timing, and characteristics of relapses in patients with GCA and to analyze whether a relapsing course is associated with disease-related complications, increased glucocorticoid (GC) doses, and GC-related adverse effects. The study cohort included 106 patients, longitudinally followed by the authors for 7.8 ± 3.3 years. Relapses were defined as reappearance of disease-related symptoms requiring treatment adjustment. Relapses were classified into 4 categories: polymyalgia rheumatica (PMR), cranial symptoms (including ischemic complications), systemic disease, or symptomatic large vessel involvement. Cumulated GC dose during the first year of treatment, time required to achieve a maintenance prednisone dose <10 mg/d (T10), <5 mg/d (T5), or complete prednisone discontinuation (T0), and GC-related side effects were recorded. Sixty-eight patients (64%) experienced at least 1 relapse, and 38 (36%) experienced 2 or more. First relapse consisted of PMR in 51%, cranial symptoms in 31%, and systemic complaints in 18%. Relapses appeared predominantly, but not exclusively, within the first 2 years of treatment, and only 1 patient developed visual loss. T10, T5, and T0 were significantly longer in patients with relapses than in patients without relapse (median, 40 vs 27 wk, p  < 0.0001; 163 vs 89.5 wk, p = 0.004; and 340 vs 190 wk, p = 0.001, respectively). Cumulated prednisone dose during the first year was significantly higher in relapsing patients (6.2 ± 1.7 g vs 5.4 ± 0.78 g, p = 0.015). Osteoporosis was more common in patients with relapses compared to those without (65% vs 32%, p = 0.001). In conclusion, the results of the present study provide evidence that a relapsing course is associated

  14. Subacromial bursitis with giant rice bodies as initial presentation of rheumatoid arthritis.

    PubMed

    Subramaniam, Ramesh; Tan, Justina Wei Lyn; Chau, Cora Yuk Ping; Lee, Keng Thiam

    2012-10-01

    Rice body formation is a nonspecific response to chronic synovial inflammation associated with tuberculous arthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, seronegative inflammatory arthritis, and even osteoarthritis. Such bodies were termed rice bodies because of their close resemblance to grains of polished white rice. We present a case report of a middle-aged woman with right shoulder subacromial/subdeltoid bursitis with giant rice body formation as her initial presentation of rheumatoid arthritis. Her right shoulder symptoms resolved after subacromial and subdeltoid bursectomy and removal of the rice bodies. She subsequently developed inflammatory arthritis of other joints, met the criteria for rheumatoid arthritis, and has been treated medically.

  15. [Breast lesions as the presenting feature of giant cell arteritis].

    PubMed

    Meriglier, E; Belhadj Chaidi, R; Debouverie, O; Luca, L; Roblot, P

    2016-08-01

    Giant cell arteritis most commonly involves the external carotid branches. Although they are less typical, extra-cephalic forms have also been reported. We report the case of a 59-year-old female patient who developed bilateral, painful breast nodules with fever and altered general status since two months. Two weeks later, she presented frontal headache and scalp tenderness. A colour duplex ultrasound of the temporal artery showed a halo sign. The results of a breast needle biopsy were inconclusive but the temporal artery biopsy confirmed the diagnosis of giant cell arteritis. The disease course was rapidly favourable after institution of corticosteroids. Breast involvement is rare but could be the first sign of giant cell arteritis. The internal mammary artery, which is a branch of the subclavian artery, can be affected and responsible for breast nodules. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  16. [Atypical presentation of a clinical case of giant cell arteritis].

    PubMed

    Rosselló Aubach, L L; Torres Cortada, G; Cabau Rúbies, J; Aragón Sanz, M A; Oncins Torres, R

    2006-06-01

    We present a very unusual clinical case of giant cell arteritis with uterus involvement, in a women of 66 years old, that began clinical features of pain and functional limitation of shoulders and hip 3 mouth before been operated of uterus prolapse with hysterectomy. Biopsy of uterus found affected arterial vesels with wall sclerosis and granulomatous inflamation with giant cells, without necrosis, involving media and perivascular portions suggesting giant cell arteritis. In a previous reports review, we only found ten similar clinical cases. In that cases, clinical features were no suggestif of the disease. Although the well known tendency of arteritis to involve some specific vascular areas, the case we present is an example of the systemic course of the disease and his difficulty to diagnose.

  17. Giant Cell Myocarditis: Not Always a Presentation of Cardiogenic Shock.

    PubMed

    Tompkins, Rose; Cole, William J; Rosenzweig, Barry P; Axel, Leon; Bangalore, Sripal; Lala, Anuradha

    2015-01-01

    Giant cell myocarditis is a rare and often fatal disease. The most obvious presentation often described in the literature is one of rapid hemodynamic deterioration due to cardiogenic shock necessitating urgent consideration of mechanical circulatory support and heart transplantation. We present the case of a 60-year-old man whose initial presentation was consistent with myopericarditis but who went on to develop a rapid decline in left ventricular systolic function without overt hemodynamic compromise or dramatic symptomatology. Giant cell myocarditis was confirmed via endomyocardial biopsy. Combined immunosuppression with corticosteroids and calcineurin inhibitor resulted in resolution of symptoms and sustained recovery of left ventricular function one year later. Our case highlights that giant cell myocarditis does not always present with cardiogenic shock and should be considered in the evaluation of new onset cardiomyopathy of uncertain etiology as a timely diagnosis has distinct clinical implications on management and prognosis.

  18. Giant Cell Myocarditis: Not Always a Presentation of Cardiogenic Shock

    PubMed Central

    Tompkins, Rose; Cole, William J.; Rosenzweig, Barry P.; Axel, Leon; Bangalore, Sripal; Lala, Anuradha

    2015-01-01

    Giant cell myocarditis is a rare and often fatal disease. The most obvious presentation often described in the literature is one of rapid hemodynamic deterioration due to cardiogenic shock necessitating urgent consideration of mechanical circulatory support and heart transplantation. We present the case of a 60-year-old man whose initial presentation was consistent with myopericarditis but who went on to develop a rapid decline in left ventricular systolic function without overt hemodynamic compromise or dramatic symptomatology. Giant cell myocarditis was confirmed via endomyocardial biopsy. Combined immunosuppression with corticosteroids and calcineurin inhibitor resulted in resolution of symptoms and sustained recovery of left ventricular function one year later. Our case highlights that giant cell myocarditis does not always present with cardiogenic shock and should be considered in the evaluation of new onset cardiomyopathy of uncertain etiology as a timely diagnosis has distinct clinical implications on management and prognosis. PMID:26257963

  19. [Corticosteroids in giant cell arteritis: primum nil nocere?].

    PubMed

    Meola, D C; Fierz, A; Tschopp, A; Landau, K

    2006-05-01

    Steroids are the treatment of choice for giant cell arteritis but bear the risk of serious side effects. We carried out a retrospective study on 34 patients with documented giant cell arteritis (24 with ocular involvement) by means of a questionnaire sent to the treating physicians. After a mean follow-up of 48 months, side effects occurred in 90 % of the patients. The most frequent were weight gain (> 50 %) and osteoporosis (> 40 %, F > M). Side effects were more common in patients with ocular involvement and in women. Severe complications were significantly more frequent in patients with ocular involvement. Side effects are the rule and not the exception in the treatment of giant cell arteritis. They can affect quality of life. Physicians should bear them in mind as many are preventable and/or treatable.

  20. A new giant titanosaur sheds light on body mass evolution among sauropod dinosaurs.

    PubMed

    Carballido, José L; Pol, Diego; Otero, Alejandro; Cerda, Ignacio A; Salgado, Leonardo; Garrido, Alberto C; Ramezani, Jahandar; Cúneo, Néstor R; Krause, Javier M

    2017-08-16

    Titanosauria was the most diverse and successful lineage of sauropod dinosaurs. This clade had its major radiation during the middle Early Cretaceous and survived up to the end of that period. Among sauropods, this lineage has the most disparate values of body mass, including the smallest and largest sauropods known. Although recent findings have improved our knowledge on giant titanosaur anatomy, there are still many unknown aspects about their evolution, especially for the most gigantic forms and the evolution of body mass in this clade. Here we describe a new giant titanosaur, which represents the largest species described so far and one of the most complete titanosaurs. Its inclusion in an extended phylogenetic analysis and the optimization of body mass reveals the presence of an endemic clade of giant titanosaurs inhabited Patagonia between the Albian and the Santonian. This clade includes most of the giant species of titanosaurs and represents the major increase in body mass in the history of Titanosauria. © 2017 The Author(s).

  1. Giant Cell Tumor within the Proximal Tibia after ACL Reconstruction.

    PubMed

    Takahashi, Takashi; MacCormick, Lauren; Ellermann, Jutta; Clohisy, Denis; Marette, Shelly

    2016-01-01

    26-year-old female with prior anterior cruciate ligament reconstruction developed an enlarging lytic bone lesion around the tibial screw with sequential imaging over the course of one year demonstrating progression of this finding, which was confirmed histologically to be a giant cell tumor of bone. The lesion originated around the postoperative bed, making the diagnosis challenging during the early course of the presentation. The case demonstrates giant cell tumor which originated in the metaphysis and subsequently grew to involve the epiphysis; therefore, early course of the disease not involving the epiphysis should not exclude this diagnosis.

  2. Giant Cell Tumor within the Proximal Tibia after ACL Reconstruction

    PubMed Central

    Takahashi, Takashi; MacCormick, Lauren; Ellermann, Jutta; Clohisy, Denis; Marette, Shelly

    2016-01-01

    26-year-old female with prior anterior cruciate ligament reconstruction developed an enlarging lytic bone lesion around the tibial screw with sequential imaging over the course of one year demonstrating progression of this finding, which was confirmed histologically to be a giant cell tumor of bone. The lesion originated around the postoperative bed, making the diagnosis challenging during the early course of the presentation. The case demonstrates giant cell tumor which originated in the metaphysis and subsequently grew to involve the epiphysis; therefore, early course of the disease not involving the epiphysis should not exclude this diagnosis. PMID:26981302

  3. IL-4 induces the formation of multinucleated giant cells and expression of β5 integrin in central giant cell lesion

    PubMed Central

    Aghbali, Amirala; Rafieyan, Sona; Mohamed-Khosroshahi, Leila; Baradaran, Behzad; Shanehbandi, Dariush

    2017-01-01

    Background It is now well established that IL-4 has a central role in the development of monocytes to multinucleated giant cells (MGCs) by inducing the expression of integrins on the surface of monocytes. The aim of this study was to investigate the potential role of IL-4 in induction of β5 integrin expression in the peripheral blood samples of patients with giant cell granuloma. Material and Methods Monocytes were isolated from peripheral blood samples of patients with central giant cell granuloma (CGCG) and healthy controls using human Monocyte Isolation Kit II. Isolated monocytes were then cultured in the absence or presence of IL-4 (10 and 20 ng/mL), and following RNA extraction and cDNA synthesis, Real-time PCR was performed to determine the level of β5 integrin expression. The formation of CGCGs and morphological analyses were done under light microscopy. For confirmation of CGCGs, immunocytochemistry technique was also carried out by anti-RANK (receptor-activator of NF-κB ligand) antibody. Results In both patient and control groups, β5 levels were significantly enhanced by increasing the IL-4 dose from 10 to 20 ng/mL. In addition, these differences were significant between patient and control groups without IL-4 treatment. On the other hand, the number of cells which expressed RANK and therefore the number of giant cells were significantly higher in the patient group in comparison to controls, as assessed by immunohistochemistry evaluations. Conclusions In this study, we showed an elevation in the expression levels of β5 integrin when stimulated by IL-4. It is strongly indicated that this integrin acts as an important mediator during macrophage to macrophage fusion and development of giant cells. Key words:β5 integrin, giant cell, Il-4, monocyte, rank. PMID:27918730

  4. Necrobiotic xanthogranuloma associated with choroidal infiltration and syncytial giant cell hepatitis.

    PubMed

    Amer, Radgonde; Pe'er, Jacob; Pappo, Orit; Dotan, Shlomo

    2005-09-01

    A 31-year-old woman developed necrobiotic xanthogranuloma (NXG), a thickened choroid, and syncytial giant cell hepatitis, a previously unreported association. NXG and syncytial giant cell hepatitis may have a common autoimmune pathogenesis.

  5. [Giant cell tumor of the lumbar spine. Case report and review of the literature].

    PubMed

    Zabalo, Gorka; Ortega, Rodrigo; Vázquez, Alfonso; Carballares, Ianire; Díaz, Jorge; Portillo, Eduardo

    2015-01-01

    We report the case of a 32-year-old patient complaining of chronic low back pain radiating to his left thigh. His MRI showed a lytic L1 vertebral body injury. A transpedicular biopsy confirmed the diagnosis of giant cell tumor. He underwent a L1 vertebrectomy and vertebral body replacement with a titanium cylinder using anterior approach, followed by the removal of the L1 posterior arch and the placement of pedicle screws through a posterior approach. The giant cell tumor is a rare benign primary bone tumor that can be locally aggressive and can potentially spread to other areas, usually to the lungs. Although it most frequently affects long bones, approximately 10% of tumors are located in the spine. To minimise the risk of recurrence, the elective management option is surgery. Copyright © 2014 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

  6. Downsizing a giant: re-evaluating Dreadnoughtus body mass.

    PubMed

    Bates, Karl T; Falkingham, Peter L; Macaulay, Sophie; Brassey, Charlotte; Maidment, Susannah C R

    2015-06-01

    Estimates of body mass often represent the founding assumption on which biomechanical and macroevolutionary hypotheses are based. Recently, a scaling equation was applied to a newly discovered titanosaurian sauropod dinosaur (Dreadnoughtus), yielding a 59 300 kg body mass estimate for this animal. Herein, we use a modelling approach to examine the plausibility of this mass estimate for Dreadnoughtus. We find that 59 300 kg for Dreadnoughtus is highly implausible and demonstrate that masses above 40 000 kg require high body densities and expansions of soft tissue volume outside the skeleton several times greater than found in living quadrupedal mammals. Similar results from a small sample of other archosaurs suggests that lower-end mass estimates derived from scaling equations are most plausible for Dreadnoughtus, based on existing volumetric and density data from extant animals. Although volumetric models appear to more tightly constrain dinosaur body mass, there remains a clear need to further support these models with more exhaustive data from living animals. The relative and absolute discrepancies in mass predictions between volumetric models and scaling equations also indicate a need to systematically compare predictions across a wide size and taxonomic range to better inform studies of dinosaur body size.

  7. Downsizing a giant: re-evaluating Dreadnoughtus body mass

    PubMed Central

    Bates, Karl T.; Falkingham, Peter L.; Macaulay, Sophie; Brassey, Charlotte; Maidment, Susannah C. R.

    2015-01-01

    Estimates of body mass often represent the founding assumption on which biomechanical and macroevolutionary hypotheses are based. Recently, a scaling equation was applied to a newly discovered titanosaurian sauropod dinosaur (Dreadnoughtus), yielding a 59 300 kg body mass estimate for this animal. Herein, we use a modelling approach to examine the plausibility of this mass estimate for Dreadnoughtus. We find that 59 300 kg for Dreadnoughtus is highly implausible and demonstrate that masses above 40 000 kg require high body densities and expansions of soft tissue volume outside the skeleton several times greater than found in living quadrupedal mammals. Similar results from a small sample of other archosaurs suggests that lower-end mass estimates derived from scaling equations are most plausible for Dreadnoughtus, based on existing volumetric and density data from extant animals. Although volumetric models appear to more tightly constrain dinosaur body mass, there remains a clear need to further support these models with more exhaustive data from living animals. The relative and absolute discrepancies in mass predictions between volumetric models and scaling equations also indicate a need to systematically compare predictions across a wide size and taxonomic range to better inform studies of dinosaur body size. PMID:26063751

  8. Giant cell arteritis associated with chronic active Epstein-Barr virus infection.

    PubMed

    Giardina, A; Rizzo, A; Ferrante, A; Capra, G; Triolo, G; Ciccia, F

    2013-03-28

    Giant cell arteritis is an inflammatory vasculopathy that preferentially affects medium-sized and large arteries. A viral cause has been suspected but not confirmed in polymyalgia rheumatica and giant-cell arteritis. We report the case of a 81-year-old female who suffered from chronic active Epstein-Barr virus infection and developed giant cell temporal arteritis.

  9. CENTRAL GIANT CELL GRANULOMA OF THE JAWS AND GIANT CELL TUMOR OF LONG BONES - AN IMMUNOHISTOCHEMICAL COMPARATIVE STUDY

    PubMed Central

    Aragão, Maria do Socorro; Piva, Marta Rabello; Nonaka, Cassiano Francisco Weege; Freitas, Roseana de Almeida; de Souza, Lélia Batista; Pinto, Leão Pereira

    2007-01-01

    Objective: This study investigated whether some components of the extracellular matrix and CD68 expression may drive the differences between the central giant cell granuloma (CGCG) of the jaws and giant cell tumor (GCT) of long bones, which present distinct evolution and clinical behavior. Material and Methods: Eight cases of CGCG and 7 cases of GCT were selected and immunohistochemically analyzed to verify the pattern of expression of CD68, tenascin (Tn) and fibronectin (Fn). Results: A large number of the mononuclear cells and multinucleated giant cells CD68+ was observed in both of the studied lesions, indicating histiocyte/macrophage origin. Seven cases of CGCG of the jaws showed intense staining of Fn, with uniform distribution predominantly. In all 7 cases of GCT of long bones the Fn displayed intense expression, with distribution pattern varying from uniform to reticulate/fibrillar. Six cases of CGCG were intensively stained by Tn, presenting focal expression in half of specimens, and reticulate/fibrillar pattern of expression in 4 cases. All cases of GCT of the long bones presented intense expression of Tn, uniform distribution, and reticulate/fibrillar pattern of expression in four cases. Conclusions: The immunoexpression of CD68 in mononuclear cells and multinucleated giant cells and staining patterns of Fn and Tn were similar in both entities. These findings indicate that these proteins could not be used to explain the differences between the CGCG of the jaws and GCT of the long bones. PMID:19089150

  10. The role of temporal artery biopsies in giant cell arteritis

    PubMed Central

    Davies, CG; May, DJ

    2011-01-01

    A knowledge of the disease process of giant cell arteritis and its diagnosis can help a surgeon to decide which patients will benefit from a biopsy being performed and identify where a biopsy would be of no value in their management. This article discusses the issues involved. PMID:21418754

  11. Reparative giant cell granuloma in a pediatric patient.

    PubMed

    Duarte Ruiz, Blanca; Riba García, Francisco de Asís; Navarro Cuéllar, Carlos; Bucci, Tommaso; Cuesta Gil, Matías; Navarro Vila, Carlos

    2007-08-01

    Reparative giant cell granulomas are benign, infrequent tumors, of non-odontogenic origin, that develop at central or peripheral level. Peripherally located lesions are frequently denominated "giant cell epulis", and never correspond to true neoplasia, but rather to inflammatory reactions secondary to another lesion (hemorrhage, etc.). It should be taken into account, that in general, head and neck tumors of infancy usually demonstrate an atypical biological behaviour. Furthermore, the anatomicopathologic diagnosis is often compromised in this type of lesion. We present the case of a 6-year-old boy, who, three weeks after suffering a slight facial trauma, developed a painless, exophytic swelling of approximately 4 cm, with bleeding on palpation, in the ipsilateral hemimaxilla. The lesion demonstrated rapid, progressive and continuous growth. The facial CT and incisional biopsy confirmed the suspected diagnosis of reparative giant cell granuloma. The patient was surgically treated, carrying out a left marginal maxillectomy associated with the extirpation of the soft-tissue lesion. The resultant defect was reconstructed with a Bichat fat-pad providing the patient with optimal esthetic and functional results. The definitive anatomicopathologic report of the surgical piece is compatible with reparative giant cell granuloma.

  12. Pediatric Upper Cervical Spine Giant Cell Tumor: Case Report

    PubMed Central

    Alfawareh, Mohammad D.; Shah, Irfanullah D.; Orief, Tamer I.; Halawani, Mohammad M.; Attia, Walid I.; Almusrea, Khaled N.

    2014-01-01

    Study Design Case report. Objective The purpose of this work is to report the case of a giant cell tumor involving the second cervical vertebra in a pediatric patient. Surgical management included a combined posterior and anterior cervical approach. There has been no recurrence in 2 years of follow-up. Case Report A 13-year-old girl presented with scoliosis with incidentally lytic lesion involving the second cervical vertebra. The radiologic investigations and biopsy result indicated a giant cell tumor of the bone. A combined posterior and anterior cervical approach was performed to resect the lesion, reconstruct the spine, and restore stability. Two years of follow-up revealed no recurrence of the lesion with stable reconstruction of the spine. Results The lesion was surgically managed for excision and spinal fusion by combining a posterior occipitocervical arthrodesis with an anterior retropharyngeal cervical approach. The final histopathology result confirmed a giant cell tumor of the bone. Conclusions Giant cell tumor involving the second cervical vertebra is uncommon; this tumor can be managed surgically by using a combined posterior and anterior cervical retropharyngeal approach. The presented case was unique in terms of the tumor location, patient age, and surgical management. PMID:26225290

  13. Liver transplant for giant cell hepatitis with autoimmune haemolytic anaemia

    PubMed Central

    Melendez, H. V.; Rela, M.; Baker, A.; Ball, C.; Portmann, B.; Mieli-Vergani, G.; Heaton, N.

    1997-01-01

    

 Giant cell hepatitis (CGH) with autoimmune haemolytic anaemia (AHA) is a distinct entity with an aggressive course. Immunosuppression may help early disease. A case is reported of a child with GCH and AHA with early disease recurrence after liver transplantation for end stage liver disease. 

 PMID:9370907

  14. Giant cell myocarditis mimicking idiopathic fascicular ventricular tachycardia.

    PubMed

    Weidenbach, Michael; Springer, Tina; Daehnert, Ingo; Klingel, Karin; Doll, Susanne; Janousek, Jan

    2008-02-01

    We report an adolescent with giant cell myocarditis (GCM) mimicking tachycardia-induced cardiomyopathy. His electrocardiogram (ECG) was typical for an incessant form of fascicular ventricular tachycardia. The patient rapidly deteriorated and required support using extracorporeal membrane oxygenation (ECMO). Biopsy revealed GCM with massive myocyte necrosis. He was successfully heart transplanted 6 days after admission.

  15. The diagnosis and classification of giant cell arteritis.

    PubMed

    Nesher, Gideon

    2014-01-01

    Giant-cell arteritis (GCA) involves the major branches of the aorta with predilection for the extracranial branches of the carotid artery. It occurs in individuals older than 50 years and the incidence increases with age. The signs and symptoms of giant cell arteritis can be classified into four subsets: cranial arteritis, extracranial arteritis, systemic symptoms and polymyalgia rheumatica. Patients may develop any combination of these manifestations, associated with laboratory evidence of an acute-phase reaction. The only test that confirms GCA diagnosis is a temporal artery biopsy, showing vasculitis with mononuclear cell inflammatory infiltrates, often with giant cells. Due to the focal and segmental nature of the infiltrates, areas of inflammation may be missed by the biopsy and the histological examination is normal in about 15% of the cases. Some imaging modalities may aid in the diagnosis of GCA. Among those, color duplex ultrasonography of the temporal arteries is more commonly used. There are no independent validating criteria to determine whether giant cell arteritis is present when a temporal artery biopsy is negative. The American College of Rheumatology criteria for the classification of giant cell arteritis may assist in the diagnosis. However, meeting classification criteria is not equivalent to making the diagnosis in individual patients, and the final diagnosis should be based on all clinical, laboratory, imaging and histological findings. Glucocorticoids are the treatment of choice for GCA. The initial dose is 40-60 mg/day for most uncomplicated cases. Addition of low-dose aspirin (100 mg/d) has been shown to significantly decrease the rate of vision loss and stroke during the course of the disease.

  16. Taking a "Giant Tour" to Explore the Human Body

    ERIC Educational Resources Information Center

    Davies, Dan

    2013-01-01

    Helping children to visualise what is inside them and how their bodies work can be a challenge, since teachers are often reliant on secondary sources or investigations that can only measure outward signs (such as pulse rate). Another way is to involve the children in an imaginative role-play exercise where they explore the insides of a…

  17. Taking a "Giant Tour" to Explore the Human Body

    ERIC Educational Resources Information Center

    Davies, Dan

    2013-01-01

    Helping children to visualise what is inside them and how their bodies work can be a challenge, since teachers are often reliant on secondary sources or investigations that can only measure outward signs (such as pulse rate). Another way is to involve the children in an imaginative role-play exercise where they explore the insides of a…

  18. Spondylectomy for Giant Cell Tumor After Denosumab Therapy

    PubMed Central

    de Carvalho Cavalcante, Rodrigo Alves; Silva Marques, Rômulo Alberto; dos Santos, Vinicius Gonçalves; Sabino, Eduardo; Fraga, Ailton Cabral; Zaccariotti, Vladimir Arruda; Arruda, Joao Batista; Fernandes, Yvens Barbosa

    2016-01-01

    Study Design. A case report. Objective. To report a case of the lumbar giant cell tumor (GCT) utilizing a new clinical treatment modality (denosumab therapy), which showed a massive tumor reduction combined with the L4 spondylectomy. Summary of Background Data. There are some controversies about spinal GCT treatments. Denosumab has provided good clinical results in terms of tumor shrinkage, and local control in a short-time follow-up clinical study phase 2, although for spinal lesions, it has not been described. Nonetheless, “en bloc” spondylectomy has been accepted as being the best treatments modalities in terms of oncological control. Methods. A case study with follow-up examination and series radiological assessments 6 months after therapy started, followed by a complex spine surgery. Results. The denosumab therapy showed on the lumbar computed tomography scans follow-up 6 months later, a marked tumor regression around 90% associated to vertebral body calcification, facilitating a successful L4 spondylectomy with an anterior and posterior reconstruction. The patient recovered without neurological deficits. Conclusion. A new therapeutic modality for spinal GCT is available and showing striking clinical results; however, it is necessary for well-designed studies to answer the real role of denosumab therapy avoiding or facilitating complex spine surgeries as spondylectomies for spinal GCT. Level of Evidence: 5 PMID:26579960

  19. Multinucleated giant cell reaction in lower lip squamous cell carcinoma: a clinical, morphological, and immunohistochemical study.

    PubMed

    Santos, Hellen Bandeira de Pontes; Miguel, Márcia Cristina da Costa; Pinto, Leão Pereira; Gordón-Núñez, Manuel Antonio; Alves, Pollianna Muniz; Nonaka, Cassiano Francisco Weege

    2017-10-01

    Multinucleated giant cell (MGC) reactions have been identified in several malignancies, but their frequency and significance in lower lip squamous cell carcinoma (SCC) are not established. This study evaluated the MGC reactions and their association with clinicopathological parameters in lower lip SCCs. The polarization profile of these cells (M1 or M2 macrophages) was also assessed. The presence and distribution of MGC reactions in high-power fields (400×) were evaluated in hematoxylin/eosin-stained histological sections of 91 lower lip SCCs. The histopathological grade of malignancy was evaluated using two grading systems (World Health Organization [WHO] and Malignancy Grading of the Deep Invasive Margins). The histiocytic nature (CD68) and polarization profile (M1-HLA-DR+ or M2-CD163+) of MGCs were evaluated by immunohistochemistry. Multinucleated giant cell reaction was identified in 36 (39.6%) cases, and its frequency was 3.3 times higher in well/moderately differentiated tumors than in poorly differentiated tumors (WHO grading system) (P = 0.006). For Malignancy Grading of the Deep Invasive Margins, the frequency was 2.03 times higher in highly/moderately keratinized tumors than in tumors with minimal/no keratinization (P = 0.012). No significant associations were observed between the presence/distribution of MGCs and clinical parameters (tumor size, lymph node metastasis, distant metastasis, and clinical stage) (P > 0.05). All MGCs were positive for CD68 and there was a predominance of HLA-DR(+) over CD163(+) MGCs (P = 0.031). Multinucleated giant cell reactions may not be involved in tumor progression in lower lip SCCs. In this microenvironment, MGCs tend to exhibit a predominantly M1 phenotype and may represent a foreign body reaction to SCC keratin pearls. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Giant cell arteritis: a multicenter observational study in Brazil

    PubMed Central

    de Souza, Alexandre Wagner Silva; Okamoto, Karine Yoshiye Kajiyama; Abrantes, Fabiano; Schau, Bruno; Bacchiega, Ana Beatriz Santos; Shinjo, Samuel Katsuyuki

    2013-01-01

    OBJECTIVE: To describe demographic features, disease manifestations and therapy in patients with giant cell arteritis from referral centers in Brazil. METHODS: A retrospective cohort study was performed on 45 giant cell arteritis patients from three university hospitals in Brazil. Diagnoses were based on the American College of Rheumatology classification criteria for giant cell arteritis or temporal artery biopsy findings. RESULTS: Most patients were Caucasian, and females were slightly more predominant. The frequencies of disease manifestations were as follows: temporal headache in 82.2%, neuro-ophthalmologic manifestations in 68.9%, jaw claudication in 48.9%, systemic symptoms in 44.4%, polymyalgia rheumatica in 35.6% and extra-cranial vessel involvement in 17.8% of cases. Aortic aneurysms were observed in 6.6% of patients. A comparison between patients with biopsy-proven giant cell arteritis and those without temporal artery biopsies did not yield significant differences in disease manifestations. All patients were treated with oral prednisone, and intravenous methylprednisolone was administered to nearly half of the patients. Methotrexate was the most commonly used immunosuppressive agent, and low-dose aspirin was prescribed to the majority of patients. Relapses occurred in 28.9% of patients, and aspirin had a protective effect against relapses. Females had higher prevalences of polymyalgia rheumatica, systemic manifestations and jaw claudication, while permanent visual loss was more prevalent in men. CONCLUSIONS: Most of the clinical features of Brazilian giant cell arteritis patients were similar to those found in other studies, except for the high prevalence of neuro-ophthalmic manifestations and permanent blindness in the Brazilian patients. Aspirin had a protective effect on relapses. PMID:23644850

  1. Ophthalmic presentation of giant cell arteritis in African-Americans.

    PubMed

    Garrity, S T; Pistilli, M; Vaphiades, M S; Richards, N Q; Subramanian, P S; Rosa, P R; Lam, B L; Osborne, B J; Liu, G T; Duncan, K E; Shin, R K; Volpe, N J; Shindler, K S; Lee, M S; Moster, M L; Tracey, E H; Cuprill-Nilson, S E; Tamhankar, M A

    2017-01-01

    PurposeTo determine the differences in the presentation of ophthalmic giant cell arteritis between African-Americans and Caucasians.MethodsThis was a multicenter retrospective case series comparing African-American patients with ophthalmic GCA to a previously published Caucasian cohort. Neuro-ophthalmic centers across the United States were contacted to provide data on African-American patients with biopsy-proven ophthalmic giant cell arteritis. The differences between African-American and Caucasian patients with respect to multiple variables, including age, sex, systemic and ophthalmic signs and symptoms, ocular ischemic lesions, and laboratory results were studied.ResultsThe Caucasian cohort was slightly older (mean=76.1 years) than the African-American cohort (mean=72.6 years, P=0.03), and there was no difference in sex distribution between the two cohorts. Headache, neck pain, and anemia were more frequent, while jaw claudication was less frequent in African-Americans (P<0.01, <0.001, 0.02, and 0.03 respectively). Acute vision loss was the most common presentation of giant cell arteritis in both groups, though it was less common in African-Americans (78 vs 98% of Caucasians, P<0.001). Eye pain was more common in African-Americans (28 vs 8% of Caucasians, P<0.01).ConclusionsThe presenting features of ophthalmic giant cell arteritis in African-Americans and Caucasians are not markedly different, although a few significant differences exist, including higher rates of headache, neck pain, anemia, and eye pain, and lower rates of jaw claudication and acute vision loss in African-Americans. Persons presenting with suspicious signs and symptoms should undergo evaluation for giant cell arteritis regardless of race.

  2. Timescales of Quartz Crystallization and the Longevity of the Bishop Giant Magma Body

    PubMed Central

    Gualda, Guilherme A. R.; Pamukcu, Ayla S.; Ghiorso, Mark S.; Anderson, Alfred T.; Sutton, Stephen R.; Rivers, Mark L.

    2012-01-01

    Supereruptions violently transfer huge amounts (100 s–1000 s km3) of magma to the surface in a matter of days and testify to the existence of giant pools of magma at depth. The longevity of these giant magma bodies is of significant scientific and societal interest. Radiometric data on whole rocks, glasses, feldspar and zircon crystals have been used to suggest that the Bishop Tuff giant magma body, which erupted ∼760,000 years ago and created the Long Valley caldera (California), was long-lived (>100,000 years) and evolved rather slowly. In this work, we present four lines of evidence to constrain the timescales of crystallization of the Bishop magma body: (1) quartz residence times based on diffusional relaxation of Ti profiles, (2) quartz residence times based on the kinetics of faceting of melt inclusions, (3) quartz and feldspar crystallization times derived using quartz+feldspar crystal size distributions, and (4) timescales of cooling and crystallization based on thermodynamic and heat flow modeling. All of our estimates suggest quartz crystallization on timescales of <10,000 years, more typically within 500–3,000 years before eruption. We conclude that large-volume, crystal-poor magma bodies are ephemeral features that, once established, evolve on millennial timescales. We also suggest that zircon crystals, rather than recording the timescales of crystallization of a large pool of crystal-poor magma, record the extended periods of time necessary for maturation of the crust and establishment of these giant magma bodies. PMID:22666359

  3. Potential enhanced ability of giant squid to detect sperm whales is an exaptation tied to their large body size

    PubMed Central

    2013-01-01

    It has been hypothesized that sperm whale predation is the driver of eye size evolution in giant squid. Given that the eyes of giant squid have the size expected for a squid this big, it is likely that any enhanced ability of giant squid to detect whales is an exaptation tied to their body size. Future studies should target the mechanism behind the evolution of large body size, not eye size. Reconstructions of the evolutionary history of selective regime, eye size, optical performance, and body size will improve the understanding of the evolution of large eyes in large ocean animals. PMID:24127991

  4. Potential enhanced ability of giant squid to detect sperm whales is an exaptation tied to their large body size.

    PubMed

    Schmitz, Lars; Motani, Ryosuke; Oufiero, Christopher E; Martin, Christopher H; McGee, Matthew D; Wainwright, Peter C

    2013-10-15

    It has been hypothesized that sperm whale predation is the driver of eye size evolution in giant squid. Given that the eyes of giant squid have the size expected for a squid this big, it is likely that any enhanced ability of giant squid to detect whales is an exaptation tied to their body size. Future studies should target the mechanism behind the evolution of large body size, not eye size. Reconstructions of the evolutionary history of selective regime, eye size, optical performance, and body size will improve the understanding of the evolution of large eyes in large ocean animals.

  5. Fibular giant cell-rich osteosarcoma virtually indistinguishable radiographically and histopathologically from giant cell tumor-analysis of subtle differentiating features.

    PubMed

    Chow, Louis T C

    2015-06-01

    Giant cell-rich osteosarcoma by its abundance of osteoclastic giant cells and paucity of tumor osteoid, leads to its easy confusion with giant cell tumor during biopsy interpretation. In this report, we describe a unique case of upper fibular metaphyseal giant cell-rich osteosarcoma in a 12-year-old boy; the radiographic and histopathologic features of the biopsy and initial resected tumor are virtually indistinguishable from conventional giant cell tumor. The tumor rapidly recurred 7 months after resection with metastasis to the groin lymph nodes, was resistant to first-line chemotherapy and pursued an aggressive course, developing disseminated metastasis to the lung, liver, pelvis, scapula and clavicle, and resulted in the death of the patient 21 months after initial presentation. The subtle features alerting one to the possibility of giant cell-rich osteosarcoma are retrospectively evaluated in comparison with cases of metaphyseal conventional giant cell tumors, four from our records and those from literature review. We conclude that the occurrence of a giant cell-rich lesion in the metaphysis of a skeletally immature individual merits careful assessment for the presence of periosteal reaction, permeative infiltrative margins, lacelike osteoid formation, high mitotic activity or Ki67 proliferative index, and extra-tumoral lymphovascular permeation, since the possibility of an aggressive lesion notably giant cell-rich osteosarcoma probably increases with the number of such features. © 2015 APMIS. Published by John Wiley & Sons Ltd.

  6. A Fraction of CD133+ CNE2 Cells Is Made of Giant Cancer Cells with Morphological Evidence of Asymmetric Mitosis

    PubMed Central

    Jiang, Qingping; Zhang, Qianbing; Wang, Shuang; Xie, Siming; Fang, Weiyi; Liu, Zhen; Liu, Jinsong; Yao, Kaitai

    2015-01-01

    CD133 has been suggested as a broad-spectrum marker for cancer stem cells(CSCs). The present study investigated the expression of CD133 in biopsy tissues of nasopharyngeal carcinoma (NPC), NPC cell lines and the immortalized cell line NP69 by immunohistochemistry, flow cytometry and qRT-PCR. CD133+ cancer cells were isolated using magnetic-activated cell sorting technology. The study demonstrated that CD133+ cells are rare in NPC tissues and cell lines and that their self-renewal and proliferation abilities are stronger than those of CD133- cells and suggested that CD133+ NPC cells have characteristics of cancer stem cells. We further observed CD133+ cancer cells using a light microscope and scanning electron microscope. Generally, CD133+ cells are small, regular and round with small microvilli. On the other hand, CD133- cells are more polymorphic and larger with long micromicrovilli. Additionally, in some fields, several giant cancer cells (GCCs) in the CD133+ cell group were identified under the light microscope. Most of them were polynuclear cells. Under the scanning electron microscope, we found indefinite regular small bodies on the surface of or surrounding the giant cancer cells, some of which appeared to be creeping out the parental cells. This phenomenon was not observed in the CD133- cell groups. Through comparison with descriptions of apoptotic bodies in the literature and from the results of the acridine orange test, we propose that some of the small bodies are daughter cells of the GCCs. This phenomenon is a mode of division of cancer cells called neosis, or budding, which is a form of reproduction for simple organisms. Budding is satisfied with the rapid speed of tumor development. GCCs could be isolated by CD133 beads because the daughter cells have stem-cell characteristics and express stem-cell markers. PMID:26535065

  7. Giant cell tumor of the femoral neck: case report.

    PubMed

    Silva, Paulo; Amaral, Rogério Andrade do; Oliveira, Leandro Alves de; Moraes, Frederico Barra de; Chaibe, Eduardo Damasceno

    2016-01-01

    The authors present the case of a patient with a giant cell tumor of the left femoral neck, with adjacent progressive invasion of bone tissue. Initial treatment was done with local curettage and autologous bone graft from fibula, electrocauterization and filling with methyl methacrylate. A local tumoral relapse was present after one year; therefore a new surgical procedure was necessary, with proximal femoral wide resection and unconventional endoprosthesis fixation. The article discusses the clinical aspects and surgical treatment. This report aimed to demonstrate the necessity to perform wide resection for giant cell tumor of the femoral neck, prioritizing total resection of the tumor and its local extension, preserving limb integrity and demonstrating the complete failure of preserving surgery in cases of femoral neck involvement.

  8. Denosumab for the treatment of giant cell tumor of the bone.

    PubMed

    Brodowicz, Thomas; Hemetsberger, Margit; Windhager, Reinhard

    2015-01-01

    Giant cell tumor of bone is typically composed of neoplastic stromal cells and non-neoplastic osteoclastic giant cells. RANK-expressing osteoclastic giant cells are recruited by RANK ligand excreted by the stromal cells, and used by these neoplastic cells to create expansion space. Denosumab specifically binds to and inhibits RANK ligand, thereby eradicating osteoclastic giant cells from the tumor and thus reducing osteolytic activity. Clinical studies reported disease stabilization and clinical benefit in terms of reduced pain and analgesics use, avoided surgeries or surgeries with less morbid procedures. Adverse events observed in patients with giant cell tumor of bone were consistent with the known safety profile of denosumab with a very low incidence of hypocalcemia and osteonecrosis. Overall, denosumab was shown to suppress osteolytic activity and slow disease progression and is thus a treatment option for patients with giant cell tumor of bone.

  9. Central Giant Cell Granuloma: A potential endodontic misdiagnosis.

    PubMed

    Seifi, Safoura; Fouroghi, Ramin

    2009-01-01

    Central Giant Cell Granulomas (CGCGs) may manifest as radiolucencies anywhere in the mandible or maxilla. In rare cases, it can appear as a localized periradicular area and mimic an endodontic lesion. This case report presents an uncommon location of CGCG which was not accurately diagnosed nor timely treated. Periodic follow ups of periapical radiolucencies after RCT are necessary. Dentists should include CGCG in differential diagnosis of lesions that are refractory to endodontic treatment. [Iranian Endodontic Journal 2009;4(4):158-60].

  10. Giant cell arteritis: a systemic disease with rare cutaneous manifestations.

    PubMed

    Baum, E W; Sams, W M; Payne, R R

    1982-06-01

    Giant cell arteritis is a systemic disease usually occurring in patients in the fifth decade or older, more often in women. Dermatologic manifestations are rare but, when found, are usually expressed as scalp ulcerations or blanching associated with gangrene of the tongue. The dermatologist should be familiar with the entity because it is often more severe when associated with scalp necrosis, and prompt intervention with corticosteroids can prevent catastrophic sequelae.

  11. Giant-cell aortitis: an unusual case of Bentall operation.

    PubMed

    Lemaire, Anaïs; Cuttone, Fabio; Caprio, Sabino; Massetti, Massimo; Galateau-Salle, Françoise

    2014-03-01

    Noninfectious ascending aortitis is a very rare cause of ascending aortic aneurysm. We report a case of the truly fortuitous finding of this rare condition in a 67-year-old man operated on for an ascending aortic aneurysm associated with dystrophic aortic valve regurgitation. Intraoperative inspection revealed dissection of the aorta just above the left main coronary artery. A modified Bentall operation was performed. The pathological diagnosis was giant cell arteritis.

  12. Giant Cell Fibroma in a Two-Year-Old Child

    PubMed Central

    Mello-Moura, Anna Carolina Volpi; Bonini, Gabriela Azevedo Vasconcelos Cunha; Del Conte Zardetto, Cristina Giovannetti; Wanderley, Marcia Turolla

    2016-01-01

    The giant cell fibroma is a benign nonneoplastic fibrous tumor of the oral mucosa. It occurs in the first three decades of life in the mandibular gingiva, predominantly, showing predilection for females. This article reports a case of giant cell fibroma in a 2-year-old girl, which is an uncommon age for this lesion. The patient was brought for treatment at the Research and Clinical Center of Dental Trauma in Primary Teeth, where practice for the Discipline of Pediatric Dentistry (Faculty of Dentistry, University of São Paulo, Brazil) takes place. During clinical examination, a tissue growth was detected on the lingual gingival mucosa of the lower right primary incisors teeth. The lesion was excised under local anesthesia and submitted to histological examination at the Oral Pathology Department of the Faculty of Dentistry, University of São Paulo, which confirmed the diagnosis of giant cell fibroma. There was no recurrence after 20 months of monitoring. This instance reinforces the importance of oral care from the very first months of life in order to enable doctors to make precocious diagnosis and offer more appropriate treatments for oral diseases, as well as to promote more efficient oral health in the community. PMID:27822394

  13. Giant Cell Reparative Granuloma of the Petrous Temporal Bone

    PubMed Central

    Williams, Joy C.; Thorell, William E.; Treves, John S.; Fidler, Mary E.; Moore, Gary F.; Leibrock, Lyal G.

    2000-01-01

    Giant cell reparative granuloma (GCRG) is an unusual, benign bone lesion that most commonly affects the maxilla and mandible; skull involvement is rare. The etiology is uncertain but may be related to trauma. GCRG is difficult to distinguish from giant cell tumor of the bone and has a lower recurrence rate. Thirteen reports of temporal bone GCRG in 11 patients have been reported. One report of a petrous GCRG in a 3-year-old girl has been identified. A 38-year-old male presented with a 2-year history of fullness in his left ear, ipsilateral hearing loss, and intermittent cacosmia. Computed tomography and magnetic resonance imaging revealed a large left-sided anterior temporal extradural mass. The patient underwent a left frontotemporal craniotomy and resection of a left temporal fossa tumor that involved the petrous and squamous parts of the temporal bone. The patient's post-operative course was uneventful, except for increased hearing loss secondary to opening of the epitympanum. Follow-up at one month revealed no other problems. Histopathology of the specimen was consistent with a giant cell reparative granuloma. ImagesFigure 1Figure 2p91-aFigure 3 PMID:17171108

  14. A Translational Study of the Neoplastic Cells of Giant Cell Tumor of Bone Following Neoadjuvant Denosumab.

    PubMed

    Mak, Isabella W Y; Evaniew, Nathan; Popovic, Snezana; Tozer, Richard; Ghert, Michelle

    2014-08-06

    Giant cell tumor of bone is a primary bone tumor that is treated surgically and is associated with high morbidity in many cases. This tumor consists of giant cells expressing RANK (receptor activator of nuclear factor-κB) and mesenchymal spindle-like stromal cells expressing RANKL (RANK ligand); the interaction of these cells leads to bone resorption. Denosumab is a monoclonal antibody that binds RANKL and directly inhibits osteoclastogenesis. Clinical studies have suggested clinical and histological improvement when denosumab was administered to patients with a giant cell tumor. However, no studies have yet examined the viability and functional characteristics of tumor cells following denosumab treatment. Specimens were obtained from six patients with a histologically confirmed giant cell tumor. Two of the patients had been treated with denosumab for six months. Primary cultures of stromal cells from fresh tumor tissue were established. Cell proliferation was measured over a two-day time course. The expression of RANKL and osteoprotegerin was analyzed with use of real-time PCR (polymerase chain reaction). Histological specimens from both patients who had completed denosumab treatment showed the absence of giant cells but persistence of stromal cells. Cell proliferation studies indicated that proliferation of stromal cells cultured from clinical specimens following denosumab treatment was approximately 50% slower than that of specimens from untreated patients. The expression of RANKL in the specimens from the treated patients was almost completely eliminated. Once the giant cell tumor tissue was no longer exposed to denosumab, the stromal cells continued to proliferate in vitro, albeit to a lesser degree. However, they also showed almost complete loss of RANKL expression. It is clear that treatment with denosumab only partially addresses the therapeutic need of patients with a giant cell tumor by wiping out the osteoclasts but leaving the neoplastic stromal cells

  15. Titan cells in Cryptococcus neoformans: cells with a giant impact.

    PubMed

    Zaragoza, Oscar; Nielsen, Kirsten

    2013-08-01

    Cryptococcus neoformans is a pathogenic yeast that commonly infects immunocompromised individuals, yet has developed multiple adaptation mechanisms to the host. Several virulence factors (capsule and melanin) have been known for many years. However, this yeast also possesses a morphogenetic program that is still not well characterized. C. neoformans has the ability to dramatically enlarge its size during infection to form 'titan cells' that can reach up to 100μm in cell body diameter, in contrast to typical size cells of 5-7μm. These titan cells pose a problem for the host because they contribute to fungal survival, dissemination to the central nervous system, and possibly even latency. In this review, we will provide an overview of these cells, covering current knowledge about their phenotypic features, mechanism of formation, and their significance during infection.

  16. Otolith shape variability and associated body growth differences in giant grenadier, Albatrossia pectoralis

    PubMed Central

    Hutchinson, Charles E.; Harris, Jeremy P.; Vulstek, Scott C.; Guthrie, Charles M.

    2017-01-01

    Fish stocks can be defined by differences in their distribution, life history, and genetics. Managing fish based on stock structure is integral to successful management of a species because fishing may affect stocks disproportionately. Genetic and environmental differences can affect the shape and growth of otoliths and these differences may be indicative of stock structure. To investigate the potential for speciation or stock structure in giant grenadier, Albatrossia pectoralis, we quantified the shape of female giant grenadier otoliths and compared body growth rates for fish with three otolith shapes; shape types were classified visually by an experienced giant grenadier age reader, and were not defined by known distribution or life history differences. We found extreme variation in otolith shape among individuals; however, the shapes were a gradation and not clearly defined into three groups. The two more extreme shapes, visually defined as “hatchet” and “comb”, were discernable based on principal component analyses of elliptical Fourier descriptors, and the “mixed” shape overlapped both of the extreme shapes. Fish with hatchet-shaped otoliths grew faster than fish with comb-shaped otoliths. A genetic test (cytochrome c oxidase 1 used by the Fish Barcode of Life Initiative) showed almost no variability among samples, indicating that the samples were all from one species. The lack of young specimens makes it difficult to link otolith shape and growth difference to life history. In addition, shape could not be correlated with adult movement patterns because giant grenadiers experience 100% mortality after capture and, therefore, cannot be tagged and released. Despite these limitations, the link between body growth and otolith shape indicates measurable differences that deserve more study. PMID:28658326

  17. Kuiper: A Discovery-class Observatory for Giant Planets, Satellites, and Small Bodies

    NASA Astrophysics Data System (ADS)

    Bell, James F.; Schneider, Nicholas M.; Brown, Michael E.; Clarke, John T.; Greenhagen, Benjamin T.; Hendrix, Amanda R.; Wong, Michael H.

    2014-11-01

    The recent Planetary Decadal identified important science goals for the study of the outer solar system. However, after the end of the Cassini and Juno missions in 2017, outer solar system science might face over a decade without new U.S. missions. The Survey thus noted the critical role that space-based telescopic observations, especially those enabling significant time-domain and target coverage, can play in advancing key planetary science questions. We propose a dedicated planetary space telescope, implementable in the Discovery program, to conduct three diverse investigations. Named after pioneering planetary astronomer Gerard P. Kuiper, the mission will address 9 of the 10 Decadal's Key Questions by studying 1) the giant planets, 2) their major satellites, and 3) the panoply of small bodies that populate the outer solar system. These three diverse investigations will enable significant advances in outer solar system science, through time-domain observations and substantial time on the targets. Advances in understanding the connections between weather and climate in giant planet atmospheres, as well as the interactions between giant planet atmospheres, satellites, and their external environments (e.g., auroral, solar wind, plumes, impacts), require consistent, well-calibrated, nearly-continuous observations spanning timescales from hours to years. Progress in understanding the ways that small outer solar system bodies can be used to understand the details of early giant planet migration requires compositional knowledge of statistically significant members of key dynamical populations. Observations with the required temporal coverage and fidelity needed to address these and many other important outer solar system Decadal science goals simply cannot be obtained from ground-based telescopes, or existing or planned space telescopes. Kuiper's combination of spatial resolution, spectral resolution, UV to near-IR coverage, and substantial time-domain sampling will

  18. Giant Cell Lesions of Lungs: A Histopathological and Morphometric Study of Seven Autopsy Cases

    PubMed Central

    Natarajan, M.; Biligi, Dayananda S; Raghupathi, A.R

    2015-01-01

    Introduction Macrophages undergo fusion to form multinucleated giant cells (MGC) in several pathologic conditions. The exact mechanism of their generation is still unclear. MGC are a common feature of granulomas that develop during various inflammatory reactions. Aim To study the histopathological features of giant cell lesions in lungs and correlate the characteristics of giant cells with other histopathological findings. Also, to determine the utility of morphometry to differentiate foreign body and Langhans MGC. Materials and Methods Seven cases were analysed. Specimen of lungs was grossed, sectioned and processed. Routinely, tissue sections were stained by Haematoxylin and Eosin (H&E) stain. Polarizing microscopy and special stains were employed in selected cases. Granulomas and MGC were counted and measured. Several other parameters like location, distribution, type and number of MGC, associated predominant inflammatory component and nature of granulomas were analysed. Results Five patterns of lesions were observed in seven cases. Aspiration pneumonia was seen in three cases (42.85%) and constituted the most common pattern. However, aspiration pneumonia as the only cause of MGC was seen in only one case (14.28%). Pulmonary tuberculosis and asteroid bodies constituted two cases (28.57%) each. Cryptococcal pneumonia and cholesterol clefts constituted one case (14.28%) each. Crypococci were demonstrated to be positively birefringent by polarized microscopy on Ziehl-Neelsen stained sections. Based on statistical analysis of morphometric data, a new index (NP index) was proposed to statistically categorize MGC into foreign body type and Langhans type. NP index value of ≤0.016 was found to be statistically significant (p<0.005) in foreign body MGC. It had high sensitivity and efficacy. Conclusion MGC may not be always associated with granulomas. The mechanisms that lead to the occurrence of MGC, independent of granuloma needs to be elucidated. Morphometry may

  19. Undifferentiated Carcinoma with Osteoclast-Like Giant Cells of the Pancreas in a Patient with New Diagnosis of Follicular Non-Hodgkin's Lymphoma.

    PubMed

    Shah, Apeksha; Khurana, Tanvi; Freid, Lauren; Siddiqui, Ali A

    2014-01-01

    Pancreatic tumors with osteoclast-like giant cells are rare, with only 50 cases published to date. We report a case of a 67-year-old male with a new diagnosis of follicular non-Hodgkin's lymphoma with an incidental pancreatic body mass on abdominal imaging. Cytology from the pancreatic mass obtained via endoscopic ultrasound-directed fine-needle aspiration (EUS-FNA) revealed an undifferentiated carcinoma with osteoclast-like giant cells.

  20. Secondary malignant giant-cell tumor of bone. Clinicopathological assessment of nineteen patients

    SciTech Connect

    Rock, M.G.; Sim, F.H.; Unni, K.K.; Witrak, G.A.; Frassica, F.J.; Schray, M.F.; Beabout, J.W.; Dahlin, D.C.

    1986-09-01

    Twenty-six patients who had a malignant giant-cell tumor of bone--a sarcoma either juxtaposed to a zone of typical benign giant-cell tumor or occurring at the site of a previously documented benign giant-cell tumor--have been seen at the Mayo Clinic. Of the twenty-six tumors, nineteen were secondary to a previous attempt at local control of a benign giant-cell tumor. All but one of these nineteen patients with a secondary tumor had received therapeutic irradiation four to thirty-nine years earlier. The nature and duration of the symptoms and the sites of predilection of the malignant giant-cell tumors were the same as for benign giant-cell tumor. Fibrosarcoma occurred three times as frequently as osteosarcoma. The best results of treatment of the secondary sarcoma were obtained with early ablation.

  1. Management of Giant cell tumor occupying the 5th metacarpal bone in 6 years old child.

    PubMed

    Al Lahham, Salim; Al Hetmi, Talal; Sharkawy, Mahmoud

    2013-01-01

    Giant cell tumor of the bone (GCTOB) is a relatively uncommon tumor of the bone. It is characterized by the presence of multinucleated giant cells. Giant-cell tumor of the bone accounts for 4-5% of primary bone tumors and ∼20% of benign bone tumors. Giant cell tumors of the hand are rare, accounting for only 2-4% of all giant cell tumors. Giant cell tumor (GCT) of the bones of the hand has some special features as compared to GCT at other sites. Because of the aggressive nature of this lesion, adequate assessment of the treatment method is required. The aim is to eradicate the disease but preserve as much hand function as possible. Methods of treatment include curettage with or without bone grafts, local resection possibly combined with reconstruction using homologous or autologous bone, amputation, and resection of one or more rays.

  2. Giant Cell Fibroma in Children: Report of Two Cases and Literature Review

    PubMed Central

    Nikitakis, Nikolaos G.; Emmanouil, Dimitris; Maroulakos, Michail P.

    2013-01-01

    ABSTRACT Background Giant cell fibroma is a type of fibrous tumour of the oral mucosa which rarely affects children under the age of 10. The purpose of this paper was to contribute two clinically and histologically documented cases of giant cell fibroma in the free gingiva of a 7 and 6 year old boys. Methods Both nodules were presented in the mandibular anterior region. In the differential diagnosis several fibrous hyperplastic lesions were considered such as traumatic fibroma, papilloma, peripheral ossifying fibroma, peripheral odontogenic fibroma, giant cell fibroma and odontogenic hamartoma. Results The lesions were removed and the histological examination revealed fibrocollagenous connective tissue with the presence of stellate giant cells which confirmed the diagnosis of giant cell fibroma. Conclusions Dentists should be aware of the existence of giant cell fibroma in children, which must be included in the differential diagnosis of nodular lesions of the gingiva and adequately diagnosed and treated by removal and histopathological examination. PMID:24422028

  3. Painful scoliosis due to superposed giant cell bone tumor and aneurysmal bone cyst in a child.

    PubMed

    Togral, Guray; Arikan, Murat; Hasturk, Askin E; Gungor, Safak

    2014-07-01

    Giant cell bone tumors are the most common precursor lesions of aneurysmal bone cysts (ABCs) developing secondarily. In giant cell bone tumors containing an explicit ABC component, the observation of the solid component of the giant cell bone tumor plays a critical role in the separation of the primary ABC. In general, ABC cases together with giant cell tumors in the bone are diagnosed histopathologically. The combination of giant cell bone tumor with superposed ABC and that of painful scoliosis with backache is rarely seen in children. In this case study, we discussed the diagnosis and the treatment of a giant cell tumor and superposed an ABC present in the fifth lumbar spine in a pediatric patient admitted to our clinic with a complaint of acute scoliotic back pain.

  4. Asymmetric cell division in polyploid giant cancer cells and low eukaryotic cells.

    PubMed

    Zhang, Dan; Wang, Yijia; Zhang, Shiwu

    2014-01-01

    Asymmetric cell division is critical for generating cell diversity in low eukaryotic organisms. We previously have reported that polyploid giant cancer cells (PGCCs) induced by cobalt chloride demonstrate the ability to use an evolutionarily conserved process for renewal and fast reproduction, which is normally confined to simpler organisms. The budding yeast, Saccharomyces cerevisiae, which reproduces by asymmetric cell division, has long been a model for asymmetric cell division studies. PGCCs produce daughter cells asymmetrically in a manner similar to yeast, in that both use budding for cell polarization and cytokinesis. Here, we review the results of recent studies and discuss the similarities in the budding process between yeast and PGCCs.

  5. Giant Cell Arteritis and Polymyalgia Rheumatica: 2016 Update

    PubMed Central

    Nesher, Gideon; Breuer, Gabriel S.

    2016-01-01

    Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are both more common among people of North European decent than among Mediterranean people. Women are 2–3 times more commonly affected. Giant cell arteritis and PMR are extremely rare before age 50 years. Polymyalgia rheumatica may be “isolated” or associated with GCA. There is increased expression of inflammatory cytokines in temporal arteries of PMR patients, without overt histological evidence of arteritis. One-third of “isolated” PMR patients have vascular uptake in positron emission tomography (PET) scans, suggesting clinically unrecognized, “hidden” GCA. Typical manifestations of GCA are headache, tenderness over temporal arteries, jaw claudication, PMR, acute vision loss, and low-grade fever. Bilateral aching of the shoulders with morning stiffness is typical for PMR. In both conditions sedimentation rate and C-reactive protein are elevated, and anemia and thrombocytosis may occur. Color duplex ultrasonography of the temporal arteries may aid in GCA diagnosis. Temporal artery biopsy showing vasculitis, often with giant cells, confirms GCA diagnosis. In cases with negative biopsy one must rely on the clinical presentation and laboratory abnormalities. The diagnosis of PMR is made primarily on clinical grounds. Other conditions that may mimic GCA or PMR must be excluded. Glucocorticoids are the treatment of choice for both conditions. Prompt treatment is crucial in GCA, to prevent irreversible complications of acute vision loss and stroke. Addition of low-dose aspirin may further prevent these complications. The average duration of treatment is 2–3 years, but some patients require a prolonged course of treatment, and some may develop disease-related or treatment-related complications. No steroid-sparing agent has been proven to be widely effective thus far, but some promising therapeutic agents are currently being studied. PMID:27824543

  6. Giant Cell Arteritis and Polymyalgia Rheumatica: 2016 Update.

    PubMed

    Nesher, Gideon; Breuer, Gabriel S

    2016-10-31

    Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are both more common among people of North European decent than among Mediterranean people. Women are 2-3 times more commonly affected. Giant cell arteritis and PMR are extremely rare before age 50 years. Polymyalgia rheumatica may be "isolated" or associated with GCA. There is increased expression of inflammatory cytokines in temporal arteries of PMR patients, without overt histological evidence of arteritis. One-third of "isolated" PMR patients have vascular uptake in positron emission tomography (PET) scans, suggesting clinically unrecognized, "hidden" GCA. Typical manifestations of GCA are headache, tenderness over temporal arteries, jaw claudication, PMR, acute vision loss, and low-grade fever. Bilateral aching of the shoulders with morning stiffness is typical for PMR. In both conditions sedimentation rate and C-reactive protein are elevated, and anemia and thrombocytosis may occur. Color duplex ultrasonography of the temporal arteries may aid in GCA diagnosis. Temporal artery biopsy showing vasculitis, often with giant cells, confirms GCA diagnosis. In cases with negative biopsy one must rely on the clinical presentation and laboratory abnormalities. The diagnosis of PMR is made primarily on clinical grounds. Other conditions that may mimic GCA or PMR must be excluded. Glucocorticoids are the treatment of choice for both conditions. Prompt treatment is crucial in GCA, to prevent irreversible complications of acute vision loss and stroke. Addition of low-dose aspirin may further prevent these complications. The average duration of treatment is 2-3 years, but some patients require a prolonged course of treatment, and some may develop disease-related or treatment-related complications. No steroid-sparing agent has been proven to be widely effective thus far, but some promising therapeutic agents are currently being studied.

  7. Tenosynovial Giant Cell Tumor Arising on the Scapular Region

    PubMed Central

    Fukuda, Asako; Ueno, Takashi; Takayama, Ryoko; Ansai, Shin-ichi; Futagami, Ayako; Kawana, Seiji

    2013-01-01

    Tenosynovial giant cell tumor (TSGCT) is a benign soft tissue tumor arising from the synovial membrane that composes the lining of joints, tendons and bursae. TSGCT is a common tumor occurring in the hands and fingers, and also consecutively in the knees, ankles, feet and hips. It is rarely found in the scapular region. To the best of our knowledge, only 2 cases arising on the upper back have been reported. This report presents the case of a 44-year-old Japanese female with a TSGCT arising on her right scapular region. PMID:24403889

  8. Alternative pharmacologic therapy for aggressive central giant cell granuloma: denosumab.

    PubMed

    Schreuder, Willem H; Coumou, Annet W; Kessler, Peter A H W; de Lange, Jan

    2014-07-01

    In the search for new pharmacologic therapies for central giant cell granuloma (CGCG), proteins that are essential to osteoclastogenesis are intriguing potential targets. In the present case report, we describe a 25-year-old patient with an aggressive CGCG of the maxilla, who was successfully treated with the antiresorptive agent denosumab, after other pharmacologic treatment had failed to achieve regression or stabilization of the tumor. Denosumab could be a promising alternative to potentially mutilating surgery for CGCG. However, more research is needed before definite conclusions can be drawn about the potential role of this agent in the treatment of CGCG.

  9. Symplastic/pseudoanaplastic giant cell tumor of the bone

    PubMed Central

    Agaram, Narasimhan; Hwang, Sinchun; Lu, Chao; Wang, Lu; Healey, John; Hameed, Meera

    2016-01-01

    Objective Giant cell tumor of bone (GCTB) is a locally aggressive primary bone tumor. Its malignant counterpart is quite rare. Rarely, a conventional GCTB shows marked nuclear atypia, referred to as symplastic/pseudoanaplastic change, which can mimic sarcomatous transformation. Recently, somatic driver mutations of histone H3.3 exclusively in H3F3A have been described in GCTB. We report a series of 9 cases of GCTB with symplastic/pseudoanaplastic change, along with analysis of H3F3A variants. Materials and methods Nine cases of GCTB with symplastic change were identified. Clinico-radiological features, morphological features, and immunohistochemical stain for Ki-67 stain were reviewed. H3F3A variants were also analyzed using Sanger sequencing. Results Histologically, conventional giant cell tumor areas with scattered foci of markedly atypical cells were seen in all of the cases and all showed rare if any Ki-67 labeling. One patient had received denosumab treatment and another radiation therapy. Radiological features were characteristic of conventional GCTB. Mutation in H3F3A (p.Gly34Trp [G34W]) was found in 6 of the 7 cases. Clinical follow-up ranged from 6 to 208 months. Local recurrences were seen in 4 cases (44 %). Conclusions GCTB with symplastic/pseudoanaplastic change is an uncommon variant of conventional GCTB, which can mimic primary sarcoma or sarcomatous transformation. These tumors possess the same missense mutation in histone H3.3 as conventional GCTB. PMID:27020452

  10. The clinical approach toward giant cell tumor of bone.

    PubMed

    van der Heijden, Lizz; Dijkstra, P D Sander; van de Sande, Michiel A J; Kroep, Judith R; Nout, Remi A; van Rijswijk, Carla S P; Bovée, Judith V M G; Hogendoorn, Pancras C W; Gelderblom, Hans

    2014-05-01

    We provide an overview of imaging, histopathology, genetics, and multidisciplinary treatment of giant cell tumor of bone (GCTB), an intermediate, locally aggressive but rarely metastasizing tumor. Overexpression of receptor activator of nuclear factor κB ligand (RANKL) by mononuclear neoplastic stromal cells promotes recruitment of numerous reactive multinucleated giant cells. Conventional radiographs show a typical eccentric lytic lesion, mostly located in the meta-epiphyseal area of long bones. GCTB may also arise in the axial skeleton and very occasionally in the small bones of hands and feet. Magnetic resonance imaging is necessary to evaluate the extent of GCTB within bone and surrounding soft tissues to plan a surgical approach. Curettage with local adjuvants is the preferred treatment. Recurrence rates after curettage with phenol and polymethylmethacrylate (PMMA; 8%-27%) or cryosurgery and PMMA (0%-20%) are comparable. Resection is indicated when joint salvage is not feasible (e.g., intra-articular fracture with soft tissue component). Denosumab (RANKL inhibitor) blocks and bisphosphonates inhibit GCTB-derived osteoclast resorption. With bisphosphonates, stabilization of local and metastatic disease has been reported, although level of evidence was low. Denosumab has been studied to a larger extent and seems to be effective in facilitating intralesional surgery after therapy. Denosumab was recently registered for unresectable disease. Moderate-dose radiotherapy (40-55 Gy) is restricted to rare cases in which surgery would lead to unacceptable morbidity and RANKL inhibitors are contraindicated or unavailable.

  11. Using time-dependent models to investigate body condition and growth rate of the giant gartersnake

    USGS Publications Warehouse

    Coates, P.S.; Wylie, G.D.; Halstead, B.J.; Casazza, M.L.

    2009-01-01

    Identifying links between phenotypic attributes and fitness is a primary goal of reproductive ecology. Differences in within-year patterns of body condition between sexes of gartersnakes in relation to reproduction and growth are not fully understood. We conducted an 11-year field study of body condition and growth rate of the giant gartersnake Thamnophis gigas across 13 study areas in the Central Valley of California, USA. We developed a priori mixed effects models of body condition index (BCI), which included covariates of time, sex and snout-vent length and reported the best-approximating models using an information theoretic approach. Also, we developed models of growth rate index (GRI) using covariates of sex and periods based on reproductive behavior. The largest difference in BCI between sexes, as predicted by a non-linear (cubic) time model, occurred during the mating period when female body condition (0.014??0.001 se) was substantially greater than males (-0.027??0.002 se). Males likely allocated energy to search for mates, while females likely stored energy for embryonic development. We also provided evidence that males use more body energy reserves than females during hibernation, perhaps because of different body temperatures between sexes. We found GRI of male snakes was substantially lower during the mating period than during a non-mating period, which indicated that a trade-off existed between searching for mates and growth. These findings contribute to our understanding of snake ecology in a Mediterranean climate. ?? 2009 The Zoological Society of London.

  12. How large are the extinct giant insular rodents? New body mass estimations from teeth and bones.

    PubMed

    Moncunill-Solé, Blanca; Jordana, Xavier; Marín-Moratalla, Nekane; Moyà-Solà, Salvador; Köhler, Meike

    2014-03-01

    The island rule entails a modification of the body size of insular mammals, a character related with numerous biological and ecological variables. From the Miocene to human colonization (Holocene), Mediterranean and Canary Islands were unaltered natural ecosystems, with paleofaunas formed with endemic giant rodents among other mammals. Our aim is to create methods to estimate the body masses of fossil island rodents and address the nature of ecological pressures driving the island rule. We created regression equations based on extant rodent data and used these to estimate the body masses of the extinct species. Our results show strong correlations between teeth, cranial and postcranial measurements and body mass, except for the length of the long bones, the transversal diameter of the distal tibia and the anteroposterior diameter of the proximal tibia, where the equations were less reliable. The use of equations obtained from a more homogeneous group (suborder and family) is preferable when analyzing the area of the first molar. The new regressions were applied to estimate the body masses of some Mediterranean and Canarian fossil rodents (Canariomys, C. bravoi 1.5 kg and C. tamarani 1 kg; Hypnomys, H. morpheus 230 g and H. onicensis 200 g; and Muscardinus cyclopeus 100 g). Our results indicate that under absence of predation, resource availability (island area) is the key factor that determines the size of the Canariomys sp. However, under presence of specialized predators (birds of prey), body size evolution is less pronounced (Hypnomys sp.).

  13. Denosumab-treated Giant Cell Tumor of Bone Exhibits Morphologic Overlap With Malignant Giant Cell Tumor of Bone.

    PubMed

    Wojcik, John; Rosenberg, Andrew E; Bredella, Miriam A; Choy, Edwin; Hornicek, Francis J; Nielsen, G Petur; Deshpande, Vikram

    2016-01-01

    Giant cell tumor (GCT) of bone is a locally aggressive benign neoplasm characterized by an abundance of osteoclastic giant cells that are induced by the neoplastic mononuclear cells; the latter express high levels of receptor activator of nuclear factor κ-B ligand (RANKL). Denosumab, a RANKL inhibitor, which is clinically used to treat GCT, leads to a marked alteration in the histologic appearance of the tumor with giant cell depletion and new bone deposition, leading to substantial histologic overlap with other primary tumors of bone. Most significantly, denosumab-treated GCT (tGCT) with abundant bone deposition may mimic de novo osteosarcoma, or GCT that has undergone malignant transformation. To histologically characterize tGCT, we identified 9 cases of GCT biopsied or resected after denosumab treatment. tGCT cases included 16 specimens from 9 patients including 6 female and 3 male individuals aged 16 to 47 (median 32) years. Duration of treatment varied from 2 to 55 months. We compared these tumors with malignant neoplasms arising in GCTs (n=9). The histology of tGCT was variable but appeared to relate to the length of therapy. All tGCTs showed marked giant cell depletion. Early lesions were highly cellular, and the combination of cellularity, atypia, and haphazard bone deposition caused the lesion to resemble high-grade osteosarcoma. Unlike de novo high-grade osteosarcoma or malignancies arising in GCT, however, tGCT showed less severe atypia, reduced mitotic activity, and lack of infiltrative growth pattern. Tumor in patients on prolonged therapy showed decreased cellularity and abundant new bone, deposited as broad, rounded cords or long, curvilinear arrays. The latter morphology was reminiscent of low-grade central osteosarcoma, but, unlike low-grade central osteosarcoma, tGCT was negative for MDM2 and again lacked an infiltrative growth pattern. Overall, tGCT may have a wide range of morphologic appearances. Because the treated tumors bear little

  14. Dedifferentiated Giant-Cell Tumor of Bone with an Undifferentiated Round Cell Mesenchymal Component

    PubMed Central

    Estrada-Villaseñor, Eréndira G.; Cortés-González, Socorro; Linares-González, Luis Miguel; González-Guzmán, Roberto; Rico-Martínez, Genaro

    2014-01-01

    The dedifferentiated giant-cell tumor of the bone is a very rare variant of the giant-cell tumor (GCT). We report the clinical, radiographic and histological findings of a dedifferentiated GCT in which the dedifferentiated component consisted of small round cells. We also comment on previously reported cases of dedifferentiated GCT, discuss the clinical implications of this dual histology, and analyze the information published about the coexistence of similar genetic abnormalities in GCT and small round cell tumors of the bone. PMID:25276319

  15. TRANSFORMATION OF MONOCYTES IN TISSUE CULTURE INTO MACROPHAGES, EPITHELIOID CELLS, AND MULTINUCLEATED GIANT CELLS

    PubMed Central

    Sutton, Jerry S.; Weiss, Leon

    1966-01-01

    The sequential transformation of chicken monocytes into macrophages, epithelioid cells, and multinucleated giant cells in vitro was studied by electron microscopy after fixation and embedment in situ. The following changes occur. In the nucleus, margination of chromatin, evident in monocytes, decreases in later forms. Nucleoli become more complex and nuclear pores increase in number. In cytoplasm, a progressive increase in volume of the ectoplasm and endoplasm occurs in culture. Lysosomes increase in number and size prior to phagocytosis. During phagocytosis (most active from 1 to 3 days of culture) lysosome depletion occurs. Lysosomes are present in greatest number and show maximal structural variation in the epithelioid and young giant cells. Aging giant cells lose lysosomes. All stages possess variably large quantities of rough-surfaced endoplasmic reticulum and free ribosomes. The Golgi apparatus, small in monocytes, increases in size and complexity. Massive accumulations of lysosomes within the Golgi apparatus of macrophages and epithelioid cells suggest that lysosomes originate there. In giant cells, multiple Golgi regions occur, often ringing the nuclei. Monocytes and macrophages have few mitochondria. Mitochondria of epithelioid cells are larger, more numerous, and may have discontinuous outer membranes. Mitochondria are most numerous in giant cells where they increase with age and become polymorphous. Cytoplasmic filaments are approximately 50 to 60 A in diameter and of indeterminate length. They occur both singly and in bundles which touch cytoplasmic vesicles and mitochondria. Few filaments occur in monocytes and macrophages. A large increase in the number of filaments occurs in epithelioid cells, where filaments (90 to 100 A) surround the cytocentrum as a distinctive annular bundle often branching into the cytoplasm. The greatest concentration of filaments occurs in aged giant cells. Pseudopodia are always present. They are short and filiform in

  16. A clinicopathological study of giant cell tumor of small bones.

    PubMed

    Yanagisawa, Michiro; Okada, Kyoji; Tajino, Takahiro; Torigoe, Tomoaki; Kawai, Akira; Nishida, Jun

    2011-11-01

    Giant cell tumor (GCT) of the small bones (small-bone GCT) is usually rare and considered somewhat different from conventional GCT. The purpose of this study was to investigate and report the clinicopathological features of 11 cases with small-bone GCT. Patient information was obtained with the help of questionnaires. X-rays and paraffin blocks obtained from several institutions were clinically, radiographically, and histologically evaluated. Small-bone GCT was observed in younger patients compared to conventional GCT; 5 of the 11 (45%) patients were below 20 years of age, whereas the corresponding figure for all GCT patients is 16% in Japan. Excessive cortical bone expansion is a special feature. There were two cases of recurrence and one case of lung metastasis; the primary lesion was in the hand for all three cases. In contrast, no primary lesion of the foot recurred or metastasized. Varying degrees of positive p63 immunostaining were observed in all examined cases (n = 9) of small-bone GCT but were negative in case of giant cell reparative granuloma (GCRG) and solid variant of aneurysmal bone cyst (ABC). One case that demonstrated high-intensity positive staining had two episodes of recurrence. Small-bone GCT tends to develop in younger patients than does conventional GCT. Primary GCTs of the hand may be biologically more aggressive than those of the feet. The p63 immunostaining may be useful not only for differential diagnosis but also for prognostication of small-bone GCT.

  17. Management of Giant Cell Tumour Radius in a Three Year old Child with an Improvised Technique

    PubMed Central

    Puri, Ajay; Gulia, Ashish; Sharma, Seema; Verma, Amit K

    2014-01-01

    Giant cell tumours of immature skeleton have a very low incidence and epi-metaphyseal location. We are presenting giant cell tumour distal radius in a skeletally immature patient; an uncontained defect with a large soft tissue component which was managed by wide excision and reconstruction with an improvised technique. PMID:25654002

  18. Dermatopathology in historical perspective: the Montgomery giant cell of lichen simplex chronicus.

    PubMed

    Rubakovic, Svetlana; Steffen, Charles

    2010-01-01

    In this short historical review, we will discuss the origin and references to the giant cell that is sometimes histopathologically present in the dermis of lichen simplex chronicus that was first described by Hamilton Montgomery, MD. A photomicrograph of the giant cell was included by Montgomery in his text Dermatopathology published in 1967. We will then provide a short biography of Montgomery.

  19. Multinuclear giant cell formation is enhanced by down-regulation of Wnt signaling in gastric cancer cell line, AGS

    SciTech Connect

    Kim, Shi-Mun; Kim, Rockki; Ryu, Jae-Hyun; Jho, Eek-Hoon; Song, Ki-Joon; Jang, Shyh-Ing; Kee, Sun-Ho . E-mail: keesh@korea.ac.kr

    2005-08-01

    AGS cells, which were derived from malignant gastric adenocarcinoma tissue, lack E-cadherin-mediated cell adhesion but have a high level of nuclear {beta}-catenin, which suggests altered Wnt signal. In addition, approximately 5% of AGS cells form multinuclear giant cells in the routine culture conditions, while taxol treatment causes most AGS cells to become giant cells. The observation of reduced nuclear {beta}-catenin levels in giant cells induced by taxol treatment prompted us to investigate the relationship between Wnt signaling and giant cell formation. After overnight serum starvation, the shape of AGS cells became flattened, and this morphological change was accompanied by decrease in Myc expression and an increase in the giant cell population. Lithium chloride treatment, which inhibits GSK3{beta} activity, reversed these serum starvation effects, which suggests an inverse relationship between Wnt signaling and giant cell formation. Furthermore, the down-regulation of Wnt signaling caused by the over-expression of ICAT, E-cadherin, and Axin enhanced giant cell formation. Therefore, down-regulation of Wnt signaling may be related to giant cell formation, which is considered to be a survival mechanism against induced cell death.

  20. Giant kidney worms in a patient with renal cell carcinoma.

    PubMed

    Kuehn, Jemima; Lombardo, Lindsay; Janda, William M; Hollowell, Courtney M P

    2016-03-07

    Dioctophyma renale (D. renale), or giant kidney worms, are the largest nematodes that infect mammals. Approximately 20 cases of human infection have been reported. We present a case of a 71-year-old man with a recent history of unintentional weight loss and painless haematuria, passing elongated erythematous tissue via his urethra. CT revealed a left renal mass with pulmonary nodules and hepatic lesions. On microscopy, the erythematous tissue passed was identified as D. renale. On subsequent renal biopsy, pathology was consistent with renal cell carcinoma. This is the first reported case of concomitant D. renale infection and renal cell carcinoma, and the second reported case of D. renale infection of the left kidney alone.

  1. Endoscopic Resection of Giant Cell Tumor of the Extensor Tendon of the Foot.

    PubMed

    Lui, Tun Hing

    2017-04-01

    The localized form of giant cell tumor of the tendon sheath is one of the most common soft tissue tumors of the foot and ankle region. It is characteristically a benign, sharply localized peritendinous fibrous mass in the synovial or tendinous spaces. The purpose of this Technical Note is to present the technical details of endoscopic resection of giant cell tumor of the extensor tendon of the foot with preservation of the tendon. It is indicated in the localized form of giant cell tumor of the extensor tendon at the foot dorsum. It is contraindicated in cases with a diffuse giant cell tumor, a giant cell tumor of the extensor tendon at the phalangeal level, or involvement of the flexor tendon.

  2. Giant cell tumour of bone in the denosumab era.

    PubMed

    van der Heijden, Lizz; Dijkstra, P D Sander; Blay, Jean-Yves; Gelderblom, Hans

    2017-03-30

    Giant cell tumour of bone (GCTB) is an intermediate locally aggressive primary bone tumour, occurring mostly at the meta-epiphysis of long bones. Overexpression of receptor activator of nuclear factor kappa-B ligand (RANKL) by mononuclear neoplastic stromal cells promotes recruitment of numerous reactive multinucleated osteoclast-like giant cells, causing lacunar bone resorption. Preferential treatment is curettage with local adjuvants such as phenol, alcohol or liquid nitrogen. The remaining cavity may be filled with bone graft or polymethylmethacrylate (PMMA) bone cement; benefits of the latter are a lower risk of recurrence, possibility of direct weight bearing and early radiographic detection of recurrences. Reported recurrence rates are comparable for the different local adjuvants (27-31%). Factors increasing the local recurrence risk include soft tissue extension and anatomically difficult localisations such as the sacrum. When joint salvage is impossible, en-bloc resection and endoprosthetic joint replacement may be performed. Local tumour control on the one hand and maintenance of a functional native joint and quality of life on the other hand are the main pillars of surgical treatment for this disease. Current knowledge and development in the fields of imaging, functional biology and systemic therapy are forcing us into a paradigm shift from a purely surgical approach towards a multidisciplinary approach. Systemic therapy with denosumab (RANKL inhibitor) or zoledronic acid (bisphosphonates) blocks, respectively inhibits, bone resorption by osteoclast-like giant cells. After use of zoledronic acid, stabilisation of local and metastatic disease has been reported, although the level of evidence is low. Denosumab is more extensively studied in two prospective trials, and appears effective for the optimisation of surgical treatment. Denosumab should be considered in the standard multidisciplinary treatment of advanced GCTB (e.g. cortical destruction, soft

  3. Osteoclasts and giant cells: macrophage–macrophage fusion mechanism

    PubMed Central

    Vignery, Agnès

    2000-01-01

    Membrane fusion is a ubiquitous event that occurs in a wide range of biological processes. While intracellular membrane fusion mediating organelle trafficking is well understood, much less is known about cell–cell fusion mediating sperm cell–oocyte, myoblast–myoblast and macrophage–macrophage fusion. In the case of mononuclear phagocytes, their fusion is not only associated with the differentiation of osteoclasts, cells which play a key role in the pathogenesis of osteoporosis, but also of giant cells that are present in chronic inflammatory reactions and in tumours. Despite the biological and pathophysiological importance of intercellular fusion events, the actual molecular mechanism of macrophage fusion is still unclear. One of the main research themes in my laboratory has been to investigate the molecular mechanism of mononuclear phagocyte fusion. Our hypothesis has been that macrophage–macrophage fusion, similar to virus–cell fusion, is mediated by specific cell surface proteins. But, in contrast with myoblasts and sperm cells, macrophage fusion is a rare event that occurs in specific instances. To test our hypothesis, we established an in vitro cell–cell fusion assay as a model system which uses alveolar macrophages. Upon multinucleation, these macrophages acquire the osteoclast phenotype. This indicates that multinucleation of macrophages leads to a specific and novel functional phenotype in macrophages. To identify the components of the fusion machinery, we generated four monoclonal antibodies (mAbs) which block the fusion of alveolar macrophages and purified the unique antigen recognized by these mAbs. This led us to the cloning of MFR (Macrophage Fusion Receptor). MFR was cloned simultaneously as P84/SHPS-1/SIRPα/BIT by other laboratories. We subsequently showed that the recombinant extracellular domain of MFR blocks fusion. Most recently, we identified a lower molecular weight form of MFR that is missing two extracellular immunoglobulin (Ig

  4. Update on the management of giant cell arteritis

    PubMed Central

    Roberts, Janet; Clifford, Alison

    2017-01-01

    Giant cell arteritis (GCA) is a large vessel vasculitis that may be associated with significant complications such as blindness, stroke, or aortic aneurysm and dissection in a subset of patients. Given the serious side effects associated with prolonged courses of glucocorticoids and frequent relapses experienced when doses are tapered, increased efforts are being dedicated to the discovery of safer and more effective therapies to control this disease. The purpose of this review is to critically evaluate the role of glucocorticoid-sparing agents in the medical management of GCA with a special focus on the most recent evidence regarding the role of biologic agents, including tocilizumab (TCZ), abatacept and ustekinumab, and other novel therapies. PMID:28491267

  5. Giant cell arteritis and polymyalgia rheumatica: an update.

    PubMed

    González-Gay, Miguel A; Pina, Trinitario

    2015-02-01

    Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are two closely related diseases in people aged 50 years and older, which are more frequently observed in Western countries. Despite being common entities, concern still exists about the epidemiology, pathogenesis, and diagnosis of both entities. New imaging techniques, such as 18 fluorodeoxyglucose-positron emission tomography, have proved to be useful in detecting large-vessel involvement in GCA. Corticosteroids are the cornerstone of the therapy in GCA and PMR. Relapses are frequent in these conditions. Unlike methotrexate and tumor necrosis factor-α antagonists, anti-interleukin-6 receptor therapy appears to be useful in patients with GCA and PMR who are refractory to corticosteroids. This review summarizes recent studies on GCA and PMR.

  6. Peripheral giant cell fibroma: A rare type of gingival overgrowth

    PubMed Central

    Shah, Monali; Rathod, Chaitali V.; Shah, Vandana

    2012-01-01

    This case report describes a rare benign tumor in a 21-year-old female was referred to the department of Periodontics, regarding areas of gingival enlargement affecting both the maxilla and mandible on the right side. She was not having any systemic and family history. Surgical excision of the lesions was carried out under local anesthetic. Histopathological examination confirmed the diagnosis of giant cell fibroma. The condition responded to surgical excision and appears to have limited growth potential. It may affect a wide spectrum of ages, but it is most commonly found in young people and can be alarming due to rapid enlargement and ulceration; so careful diagnosis is important to avoid unnecessary aggressive treatment. PMID:23055599

  7. Case Study: Giant Cell Arteritis with Vertebral Artery Stenosis

    PubMed Central

    Daniel Chomlak, R.; Ghazanfari, Farshad; Datta, Mineesh

    2016-01-01

    In giant cell arteritis (GCA), involvement of the vertebral arteries is rare with reported rates of 3%–4% for ischemic events secondary to vertebral artery stenosis or occlusion for those patients with GCA. This case study describes a patient who initially presented with acute onset of vertigo but was also found to have transient, side-alternating upper limb neurological findings. While initial imaging showed no vascular abnormalities, it was not until GCA was eventually confirmed with a temporal artery biopsy that the initial scans were shown to have bilateral narrowing of the vertebral arteries. While rare, vertebral artery involvement is an important complication to consider in the setting of GCA due to the high rate of associated mortality, despite immunosuppressive therapy. PMID:27279753

  8. Giant cell reparative granuloma of the sphenoid bone.

    PubMed

    Aralasmak, A; Aygun, N; Westra, W H; Yousem, D M

    2006-09-01

    We present 2 patients with giant cell reparative granuloma (GCRG) of the sphenoid bone. The first patient is an 8-year-old boy with involvement of the greater wing, and the second is a 53- year-old man with a lateral pterygoid plate mass. Both patients presented with rapid expansion of lytic bone lesions, which had solid and cystic components and lacked matrix calcification. Biopsies were indeterminate for definitive diagnoses. The radiologic appearance, location, and incidence of the lesions, and the patient's age and medical history are helpful aids in narrowing the differential diagnosis of sphenoid bone lesions. However, the imaging and, occasionally, even the histologic findings may not suggest the specific diagnosis of GCRG, which must be added into the differential diagnosis of rapidly enlarging cystic bone lesions of the sphenoid bone.

  9. Update on the management of giant cell arteritis.

    PubMed

    Roberts, Janet; Clifford, Alison

    2017-04-01

    Giant cell arteritis (GCA) is a large vessel vasculitis that may be associated with significant complications such as blindness, stroke, or aortic aneurysm and dissection in a subset of patients. Given the serious side effects associated with prolonged courses of glucocorticoids and frequent relapses experienced when doses are tapered, increased efforts are being dedicated to the discovery of safer and more effective therapies to control this disease. The purpose of this review is to critically evaluate the role of glucocorticoid-sparing agents in the medical management of GCA with a special focus on the most recent evidence regarding the role of biologic agents, including tocilizumab (TCZ), abatacept and ustekinumab, and other novel therapies.

  10. Tongue necrosis as first symptom of giant cell arteritis (GCA).

    PubMed

    Brodmann, M; Dorr, A; Hafner, F; Gary, T; Pilger, E

    2009-06-01

    Giant cell arteritis (GCA) is the most common systemic vasculitis affecting people over the age of 50 years, especially in the western world. Nevertheless, the initial diagnosis can be tricky, as some of the patients present at first time with a real unusual initial manifestation. One of these can be tongue necrosis, which is according to the literature in accordance with scalp necrosis, the rarest initial manifestation form of GCA. We describe two patients who presented with tongue necrosis as initial symptom of GCA. The diagnosis was made by the American College of Rheumatology criteria, biopsy and duplex sonography of their temporal arteries. A typical halo was seen as a sign of intimal edema. The patients were put on corticosteroids immediately after diagnosis was proven and their symptoms improved quickly.

  11. Clinical study of giant cell arteritis in our hospital.

    PubMed

    Suematsu, Eiichi; Miyamura, Tomoya; Nakamura, Masataka; Higuchi, Makiko; Mori, Shunsuke; Iwanaga, Tomoaki; Kaku, Yu; Takahama, Soichiro; Minami, Rumi; Yamamoto, Masahiro

    2015-01-01

    To investigate clinical and laboratory features of giant cell arteritis (GCA). We included 24 patients (6 men, 18 women; mean age 69.8 years) in this study. GCA was diagnosed based on the American College of Rheumatology 1990 classification criteria. Mean serum C-reactive protein was 9.03 mg/dl. GCA was classified into three types: classic temporal arteritis type (cranial GCA, nine patients); large-vessel type, affecting the aorta and its major branches without temporal arteries (12 patients); generalized type, affecting both temporal arteries and large vessels (three patients). Swelling and tenderness of temporal arteries were recognized in temporal arteritis and generalized arteritis. Ten of these patients also had histopathologic findings of arteritis, including giant cells in biopsy specimens. Examination of HLA-class 1 expression showed that one patient with cranial GCA, three with generalized GCA, and seven with large-vessel GCA were positive for HLA-A24, and four patients with large-vessel GCA were positive for HLA-B39. One patient with cranial GCA, one with generalized GCA, and six with large-vessel GCA were positive for HLA-B52. Nine patients were positive for anti-phospholipid antibodies (seven for anti-cardiolipin antibody immunoglobulin G, seven for anti-cardiolipin β2-glycoprotein-1 antibody, one for lupus anticoagulant). Our study demonstrated that HLA-class 1 expression in GCA resembles that in Takayasu arteritis, suggesting that these two arteritis types share the same genetic background. In contrast, the difference in the prevalence of anti-phospholipid antibodies in GCA and Takayasu arteritis patients shows a difference in the characteristic aspects of these two arteritis types.

  12. Varicella zoster virus triggers the immunopathology of giant cell arteritis.

    PubMed

    Gilden, Don; Nagel, Maria A

    2016-07-01

    Giant cell arteritis (GCA) is a severe form of vasculitis in the elderly. The recent discovery of varicella zoster virus (VZV) in the temporal arteries and adjacent skeletal muscle of patients with GCA, and the rationale and strategy for antiviral and corticosteroid treatment for GCA are reviewed. The clinical features of GCA include excruciating headache/head pain, often with scalp tenderness, a nodular temporal arteries and decreased temporal artery pulsations. Jaw claudication, night sweats, fever, malaise, and a history of polymyalgia rheumatica (aching and stiffness of large muscles primarily in the shoulder girdle, upper back, and pelvis without objective signs of weakness) are common. ESR and CRP are usually elevated. Diagnosis is confirmed by temporal artery biopsy which reveals vessel wall damage and inflammation, with multinucleated giant cells and/or epithelioid macrophages. Skip lesions are common. Importantly, temporal artery biopsies are pathologically negative in many clinically suspect cases. This review highlights recent virological findings in temporal arteries from patients with pathologically verified GCA and in temporal arteries from patients who manifest clinical and laboratory features of GCA, but whose temporal artery biopsies (Bx) are pathologically negative for GCA (Bx-negative GCA). Virological analysis revealed that VZV is present in most GCA-positive and GCA-negative temporal artery biopsies, mostly in skip areas that correlate with adjacent GCA pathology. The presence of VZV in Bx-positive and Bx-negative GCA temporal arteries indicates that VZV triggers the immunopathology of GCA. However, the presence of VZV in about 20% of temporal artery biopsies from non-GCA postmortem controls also suggests that VZV alone is not sufficient to produce disease. Treatment trials should be performed to determine if antiviral agents confer additional benefits to corticosteroids in both Bx-positive and Bx-negative GCA patients. These studies should

  13. Multinucleate Giant Cells in FNAC of Benign Breast Lesions: Its Significance

    PubMed Central

    R, Kalyani; Murthy V, Srinivasa

    2014-01-01

    Background: Multinucleate giant cells are described in breast aspirates. However, due to its rarity very few cases have been described cytologically. Hence recognition and correct interpretation of their presence is difficult, yet crucial for accurate diagnosis. Materials and Methods: The prospective study of FNAC (fine needle aspirate cytology) of breast lumps was conducted for a period of six months. Direct smears were prepared from the material aspirated. In case of fluid aspirates, centrifuge done and cell sediment was used for making smears. Smears were alcohol fixed and stained with PAP/H&E or air dried smears were stained with Leishman stain. Further smears were subjected to immunocytochemistry using vimentin and CD34 markers to know the origin of multinucleate giant cells. Results: We have reported 11 cases of breast lesions, which showed multinucleate giant cells on FNAC. Out of the 11 cases, Cytologically six cases showed granuloma debris with relative proportion of epithelioid histiocytes, lymphocytes, neutrophils and multinucleate giant cells. Two cases were diagnosed as acute suppurative granulomatous mastitis. Two cases of fibroadenoma and one case of fat necrosis showed multinucleate giant cells. Immunocytochemistry showed vimentin positivity in both stromal and histiocytic type of multinucleate giant cells and in isolated histiocytes. CD34 was focally positive in histiocytic type of giant cells. Conclusion: An effort is made to distinguish between the stromal and histiocytic type giant cells in non-neoplastic breast lesions. Further molecular studies have to be done to know the exact histogenesis and role of these multinucleate giant cells in benign lesions. PMID:25653953

  14. Surgical treatment of subependymal giant cell astrocytoma in tuberous sclerosis complex patients.

    PubMed

    Kotulska, Katarzyna; Borkowska, Julita; Roszkowski, Marcin; Mandera, Marek; Daszkiewicz, Paweł; Drabik, Krzysztof; Jurkiewicz, Elzbieta; Larysz-Brysz, Magdalena; Nowak, Katarzyna; Grajkowska, Wiesława; Domańska-Pakieła, Dorota; Jóźwiak, Sergiusz

    2014-04-01

    Subependymal giant cell astrocytoma is a brain tumor associated with tuberous sclerosis complex. There are two treatment options for subependymal giant cell astrocytomas: surgery or mammalian target of rapamycin inhibitor. The analysis of outcome of subependymal giant cell astrocytoma surgery may help characterize the patients who may benefit from pharmacotherapy. Sixty-four subependymal giant cell astrocytoma surgeries in 57 tuberous sclerosis complex patients with at least a 12-month follow-up were included in the study. The tumor size, age of the patients, mutation in the TSC1 or TSC2 gene, indication for the surgery, and postsurgical complications were analyzed. The mean age of patients at surgery was 9.7 years. Mean follow-up after surgery was 63.7 months. Thirty-seven (57.8%) tumors were symptomatic and 27 (42.2%) were asymptomatic. Patients with TSC2 mutations developed subependymal giant cell astrocytoma at a significantly younger age than individuals with TSC1 mutations. Four patients (6.2% of all surgeries) died after surgery. Surgery-related complications were reported in 0%, 46%, 83%, 81%, and 67% of patients with tumors <2 cm, between 2 and 3 cm, between 3 and 4 cm, >4 cm, and bilateral subependymal giant cell astrocytomas, respectively, and were most common in children younger than 3 years of age. The most common complications included hemiparesis, hydrocephalus, hematoma, and cognitive decline. Our study indicates that subependymal giant cell astrocytoma surgery is associated with significant risk in individuals with bilateral subependymal giant cell astrocytomas, tumors bigger than 2 cm, and in children younger than 3 years of age. Therefore, tuberous sclerosis complex patients should be thoroughly screened for subependymal giant cell astrocytoma growth, and early treatment should be considered in selected patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Pathogenesis of giant cell arteritis: new insight into the implication of CD161+ T cells.

    PubMed

    Samson, M; Audia, S; Martin, L; Janikashvili, N; Bonnotte, B

    2013-01-01

    Giant cell arteritis (GCA) is a granulomatous large-vessel vasculitis that usually affects the aorta and/or its major branches, especially the branches of the carotid arteries. Histo-pathological lesions are observed in all layers of the artery leading to segmental and focal panarteritis with a polymorphic cell infiltrate that includes T cells, macrophages and multinucleated giant cells, a fragmented internal elastic lamina and intimal hyperplasia. The pathophysiology of GCA is complex and not fully understood. In this review, we discuss the immunological aspects of GCA pathogenesis with a particular emphasis on T cell responses. Upon dendritic cell activation in the adventitia, CD4 T cells co-expressing CD161 are recruited in the arterial wall and polarised into Th1 and Th17 cells that produce IFN-γ and IL-17, respectively. These cytokines activate macrophages, giant cells and vascular smooth muscle cells, thus inducing vascular remodelling which leads to the ischaemic manifestations of GCA. Macrophages infiltrating the adventitia produce IL-1β and IL-6, which are responsible for the general symptoms encountered in GCA.

  16. Establishment and cryopreservation of a giant panda skeletal muscle-derived cell line.

    PubMed

    Yu, Fang-Jian; Zeng, Chang-Jun; Zhang, Yan; Wang, Cheng-Dong; Xiong, Tie-Yi; Fang, Sheng-Guo; Zhang, He-Min

    2015-06-01

    The giant panda Ailuropoda melanoleuca is an endangered species and is a symbol for wildlife conservation. Although efforts have been made to protect this rare and endangered species through breeding and conservative biology, the long-term preservation of giant panda genome resources (gametes, tissues, organs, genomic libraries, etc.) is still a practical option. In this study, the giant panda skeletal muscle-derived cell line was successfully established via primary explants culture and cryopreservation techniques. The population doubling time of giant panda skeletal cells was approximately 33.8 h, and this population maintained a high cell viability before and after cryopreservation (95.6% and 90.7%, respectively). The two skeletal muscle-specific genes SMYD1 and MYF6 were expressed and detected by RT-PCR in the giant panda skeletal muscle-derived cell line. Karyotyping analysis revealed that the frequencies of giant panda skeletal muscle cells showing a chromosome number of 2n=42 ranged from 90.6∼94.2%. Thus, the giant panda skeletal muscle-derived cell line provides a vital resource and material platform for further studies and is likely to be useful for the protection of this rare and endangered species.

  17. Magnetic resonance imaging findings of undifferentiated carcinoma with osteoclast-like giant cells of pancreas.

    PubMed

    Yang, Kyung Yoon; Choi, Joon-Il; Choi, Moon Hyung; Park, Michael Yong; Rha, Sung Eun; Byun, Jae Young; Jung, Eun Sun; Lall, Chandana

    2016-01-01

    Undifferentiated carcinoma with osteoclast-like giant cells is a rare pancreatic and periampullary neoplasm with less than 50 cases reported in the literature. Pathologically, this tumor mimics a giant cell tumor in bones. We report a case of undifferentiated carcinoma with osteoclast-like giant cells in a 55-year-old man presenting as a pancreatic mass with associated regional and distant lymphadenopathy. On T1- and T2-weighted images, the mass shows dark signal intensity which was atypical for a pancreatic adenocarcinoma.

  18. Giant cell tumor of the humeral head treated by denosumab: Implication to shoulder surgeons

    PubMed Central

    Leung, Ka Hei; Lam, Albert Ying Lee; Ho, Kenneth Wai Yip; Shek, Tony Wai Hung

    2015-01-01

    Giant cell tumor is a benign bone tumor that is commonly encountered. The optimal treatment of a giant cell tumor which causes extensive bony destruction is controversial. Recent studies on the receptor activator of nuclear factor κB ligand antagonist denosumab may offer a new treatment option for these patients. We presented a patient with giant cell tumor of the humeral head. He was initially treated with denosumab and subsequently with the operation. The shoulder joint was successfully salvaged. But there are potential difficulties that surgeons may face in patients treated with denosumab. PMID:26622131

  19. Transgenic rice seeds accumulating recombinant hypoallergenic birch pollen allergen Bet v 1 generate giant protein bodies.

    PubMed

    Wang, Shuyi; Takahashi, Hideyuki; Kajiura, Hiroyuki; Kawakatsu, Taiji; Fujiyama, Kazuhito; Takaiwa, Fumio

    2013-06-01

    A versatile hypoallergenic allergen derivative against multiple allergens is an ideal tolerogen for allergen-specific immunotherapy. Such a tolerogen should exhibit high efficacy, without side effects, when administered at high doses and should be applicable to several allergens. Tree pollen chimera 7 (TPC7), a hypoallergenic Bet v 1 tolerogen against birch pollen allergy, was previously selected by DNA shuffling of 14 types of Fagales tree pollen allergens. In this study, transgenic rice seed accumulating TPC7 was generated as an oral vaccine against birch pollen allergy by expressing this protein as a secretory protein using the N-terminal signal peptide and the C-terminal KDEL tag under the control of an endosperm-specific glutelin promoter. The highest level of TPC7 accumulation was approximately 207 µg grain(-1). Recombinant TPC7 is a glycoprotein with high mannose-type N-glycan, but without β1,2-xylose or α1,3-fucose, suggesting that TPC7 is retained in the endoplasmic reticulum (ER). TPC7 is deposited as a novel, giant spherical ER-derived protein body, >20 µm in diameter, which is referred to as the TPC7 body. Removal of the KDEL retention signal or mutation of a cysteine residue resulted in an alteration of TPC7 body morphology, and deletion of the signal peptide prevented the accumulation of TPC7 in rice seeds. Therefore, the novel TPC7 bodies may have formed aggregates within the ER lumen, primarily due to the intrinsic physicochemical properties of the protein.

  20. Treatment of tenosynovial giant cell tumor and pigmented villonodular synovitis.

    PubMed

    Ravi, Vinod; Wang, Wei-Lien; Lewis, Valerae O

    2011-07-01

    To review recent developments in the molecular pathogenesis of tenosynovial giant cell tumor (TGCT) or pigmented villonodular synovitis (PVNS) and its therapeutic implications. TGCT or PVNS is a benign clonal neoplastic proliferation arising from the synovium characterized by a minor population of intratumoral cells that harbor a recurrent translocation. These cells overexpress CSF1, resulting in recruitment of CSF1R-bearing macrophages that are polyclonal and make up the bulk of the tumor. Inhibition of CSF1R using small molecule inhibitors such as imatinib, nilotinib or sunitinib can result in clinical, radiological and functional improvement in the affected joint. Currently, surgery remains the treatment of choice for patients with TGCT/PVNS. Localized TGCT/PVNS is managed by marginal excision. Recurrences occur in 8-20% of patients and are easily managed by re-excision. Diffuse TGCT/PVNS tends to recur more often (33-50%) and has a much more aggressive clinical course. Patients are often symptomatic and require multiple surgical procedures during their lifetime. For patients with unresectable disease or multiple recurrences, systemic therapy using CSF1R inhibitors may help delay or avoid surgical procedures and improve functional outcomes.

  1. Symptomatic giant peritoneal loose body in the pelvic cavity: A case report

    PubMed Central

    Elsner, Andreas; Walensi, Mikolaj; Fuenfschilling, Maya; Rosenberg, Robert; Mechera, Robert

    2016-01-01

    Introduction Giant peritoneal loose bodies (gPLB) occur rarely and therefore only few have been described. Often they are found incidentally and have no clinical relevance, whereas symptomatic forms may require surgical removal. Presentation of case We report the case of a male patient suffering from abdominal discomfort with alternating localizations for several years, actually presenting with a proctitis. With elevated inflammatory markers, a conspicuous resistance in the lower abdomen and in order to evaluate further affection of the colon, an abdominal CT-scan was performed. It revealed a spherical mass in the lesser pelvis. A colonoscopy confirmed the proctitis, showing no further pathologies. Due to the symptoms and the uncertain entity of the mass, a diagnostic laparoscopy was performed and a boiled egg-like structure (diameter 5.2 cm) was removed. The patient recovered well and was free of symptoms. Discussion The patient had two potential reasons for his symptoms, one of them being a suspected leftover foreign body years after an appendectomy. The proctitis was treated conservatively but without complete remission of the abdominal discomfort. Therefore, a diagnostic laparoscopy was performed and the mass turned out to be a gPLB. Conclusion To obtain a fast diagnosis and to perform an adequate conservative or surgical therapy, the knowledge about the rare entity of a gPLB is necessary. An exact anamnesis, clinical examination and the knowledge about the diagnostic values of radiological and endoscopic investigations are crucial. PMID:26901087

  2. Giant cell angiofibroma of the oral cavity: A case report and review of the literature.

    PubMed

    de Andrade, Cleverton Roberto; Lopes, Márcio Ajudarte; de Almeida, Oslei Paes; León, Jorge Esquiche; Mistro, Florence; Kignel, Sergio

    2008-09-01

    Giant cell angiofibroma is a well-circumscribed, normally encapsulated, distinctive orbital soft tissue tumor. However, it is now recognized that this lesion can also present in other locations, including the oral cavity. The morphological hallmark is a richly vascularized, patternless spindle cell proliferation containing pseudovascular spaces and floret-type multinucleate giant cells. CD34 immunoreactivity, although not specific, represents the only immunohistochemical finding of potential diagnostic value. We present a case of a 44-year-old male Caucasian patient complaining of painless solitary nodule arising on the right buccal mucosa, which was diagnosed as giant cell angiofibroma. To the best of our knowledge, this is the third case of oral giant cell angiofibroma reported in the English-language literature.

  3. Induction of giant cells by the synthetic food colorants viz. lemon yellow and orange red.

    PubMed

    Prajitha, V; Thoppil, John E

    2016-05-01

    Cytotoxicity and giant cell formation induced by lemon yellow and orange red synthetic food colorants were evaluated in the present study. The aqueous solutions of both the dye solutions were tested for cytotoxicity using Allium cepa assay. Frequency of giant cells were determined after treating the root tips with different concentrations of both food colorant solutions viz., 0.005, 0.01, 0.05, 0.1 % for varying time durations (1/2, 1, 2, 3 h). These colorants may cause giant cell formation primarily by interfering with the normal course of mitosis. Giant cells showing multiple aberrations viz. bridged and binucleate condition, cellular fragmentation, nuclear lesion, double and multiple nuclear lesions, double nuclear peaks and cellular breakage, elongated nucleus, nuclear budding, hyperchromasia, micronucleus, nuclear erosion, pulverized nucleus etc. were induced in root tips treated with both of the colorants. The synthetic food colorant treated cells showed inhibition of cell division and induction of giant cells. A dose dependant decrease in the mitotic index [88.20 % (c(-ve), 3h) to 81.54 % (Lx4, 3h) and 88.20 % (c(-ve), 3h) to 73.17 % (Ox4, 3h)] was observed. All mitotic phases show significant induction of giant cells when treated with both food colorants. Interphase stage shows higher percentage of giant cells, whereas in cytokinesis it was negligible. The orange red food colorant is observed to be more toxic because it recorded higher percentage of giant cell induction when compared with lemon yellow [27.93 % (Lx4, 3h) and 28.07 % (Ox4, 3h)].

  4. Photoinduced Giant Dielectric Constant in Lead Halide Perovskite Solar Cells.

    PubMed

    Juarez-Perez, Emilio J; Sanchez, Rafael S; Badia, Laura; Garcia-Belmonte, Germá; Kang, Yong Soo; Mora-Sero, Ivan; Bisquert, Juan

    2014-07-03

    Organic-inorganic lead trihalide perovskites have emerged as an outstanding photovoltaic material that demonstrated a high 17.9% conversion efficiency of sunlight to electricity in a short time. We have found a giant dielectric constant (GDC) phenomenon in these materials consisting on a low frequency dielectric constant in the dark of the order of ε0 = 1000. We also found an unprecedented behavior in which ε0 further increases under illumination or by charge injection at applied bias. We observe that ε0 increases nearly linearly with the illumination intensity up to an additional factor 1000 under 1 sun. Measurement of a variety of samples of different morphologies, compositions, and different types of contacts shows that the GDC is an intrinsic property of MAPbX3 (MA = CH3NH3(+)). We hypothesize that the large dielectric response is induced by structural fluctuations. Photoinduced carriers modify the local unit cell equilibrium and change the polarizability, assisted by the freedom of rotation of MA. The study opens a way for the understanding of a key aspect of the photovoltaic operation of high efficiency perovskite solar cells.

  5. Polyomavirus (BK)-associated pleomorphic giant cell carcinoma of the urinary bladder: a case report.

    PubMed

    Alexiev, Borislav A; Papadimitriou, John C; Chai, Toby C; Ramos, Emilio; Staats, Paul N; Drachenberg, Cinthia B

    2013-04-01

    This report describes the morphological features of a pleomorphic giant cell carcinoma with focal trophoblastic differentiation of the urinary bladder in a male, 12 years post living related donor renal transplant. The voided urine cytology demonstrated rare decoy cells admixed with markedly atypical urothelial cell clusters, papillae and giant cells. Cystoprostatectomy demonstrated a nodular mass involving the trigone and right lateral-posterior wall, adjacent to the ureteral orifice. Hematoxylin-eosin stained sections showed two synchronous malignancies: (a) pleomorphic giant cell carcinoma with focal trophoblastic differentiation of the urinary bladder, metastatic to the omentum and (b) prostatic adenocarcinoma, Gleason score 3+4=7, involving the right prostate lobe. Strong diffuse expression of polyomavirus large T antigen was demonstrated in the primary and metastatic pleomorphic giant cell carcinoma, supporting a possible role for polyomavirus (BK) in the oncogenetic pathway. The prostatic adenocarcinoma was negative for polyomavirus large T antigen. Our findings of p63, CK7 and CK903 expression in pleomorphic giant cell carcinoma suggest that the tumor is of urothelial derivation. This is the first report describing the morphological features of urinary bladder pleomorphic giant cell carcinoma with trophoblastic differentiation, positive for polyomavirus large T antigen, arising in the background of BKV reactivation.

  6. Florid cemento-osseous dysplasia and peripheral giant cell granuloma in a patient with neurofibromatosis 1.

    PubMed

    Sarmento, Dmitry José de Santana; Carvalho, Sérgio Henrique Gonçalves de; Araújo, José Cadmo Wanderley Peregrino de; Carvalho, Marianne de Vasconcelos; Silveira, Éricka Janine Dantas da

    2017-01-01

    We report a 35-year-old mulatto female patient with neurofibromatosis Type 1 who presented with facial asymmetry. The patient had two lesions: florid cemento-osseous dysplasia associated with peripheral giant cell granuloma. She was referred for surgical treatment of the peripheral giant cell granuloma and the florid cemento-osseous dysplasia was treated conservatively by a multidisciplinary team. So far, no changes have been observed in the patient's clinical status. We observed no recurrence of peripheral giant cell granuloma. To the best of our knowledge, the present case is the first report of a patient with neurofibromatosis Type 1 associated with a giant cell lesion and florid cemento-osseous dysplasia.

  7. Florid cemento-osseous dysplasia and peripheral giant cell granuloma in a patient with neurofibromatosis 1*

    PubMed Central

    Sarmento, Dmitry José de Santana; de Carvalho, Sérgio Henrique Gonçalves; de Araújo Filho, José Cadmo Wanderley Peregrino; Carvalho, Marianne de Vasconcelos; da Silveira, Éricka Janine Dantas

    2017-01-01

    We report a 35-year-old mulatto female patient with neurofibromatosis Type 1 who presented with facial asymmetry. The patient had two lesions: florid cemento-osseous dysplasia associated with peripheral giant cell granuloma. She was referred for surgical treatment of the peripheral giant cell granuloma and the florid cemento-osseous dysplasia was treated conservatively by a multidisciplinary team. So far, no changes have been observed in the patient's clinical status. We observed no recurrence of peripheral giant cell granuloma. To the best of our knowledge, the present case is the first report of a patient with neurofibromatosis Type 1 associated with a giant cell lesion and florid cemento-osseous dysplasia. PMID:28538890

  8. Case report 207: Giant cell reparative granuloma of left femur arising in polyostatic fibrous dysplasia

    SciTech Connect

    De Smet, A.A.; Travers, H.; Neff, J.R.

    1982-08-01

    Diagnosis and differential diagnosis of lytic lesions in the femur are discussed. Roentgenograms, a tomogram and pathological studies of a giant cell reparative granuloma of left femur arising in polyostotic fibrous dysplasia are presented.

  9. Acute Carpal Tunnel Syndrome Caused by Diffuse Giant Cell Tumor of Tendon Sheath: A Case Report

    PubMed Central

    Ward, Christina M; Lueck, Nathan E; Steyers, Curtis M

    2007-01-01

    A 46 year old male developed spontaneous acute carpal tunnel syndrome of the right wrist without any antecedent trauma. Surgical exploration revealed hemorrhage secondary to diffuse giant cell tumor of tendon sheath as the underlying cause. PMID:17907439

  10. Eruption triggering of giant magma bodies by internal versus external forcing: A rhyolite-MELTS study

    NASA Astrophysics Data System (ADS)

    Carley, T. L.; Gualda, G. A.; Ghiorso, M. S.; Miller, C. F.

    2012-12-01

    Silicic volcanism, particularly supereruptions, raises questions about the mechanisms by which magma bodies destabilize and erupt. Are external events necessary to initiate an eruption of a large silicic system, or is possible for internal processes (crystallization, volatile exsolution) to destabilize a system and drive it to erupt? If external triggers are critically important to prompting eruption, are all felsic magma bodies equally prone to erupt? To respond to these questions, we use rhyolite-MELTS (Gualda et al. 2012) to investigate the pre-eruptive chemical evolution and the resultant changes to physical properties of giant (super-eruptive) felsic magma bodies. Simulations are conducted using pumice and glass compositions from the Peach Spring (Southwestern USA) and the Bishop (California USA) Tuffs, two giant high-silica rhyolite deposits. In our simulations, we vary initial pressure (150-350 MPa in 50 MPa intervals), volatile content (initial water ranging from 1-7 wt. %), mode of crystallization (equilibrium vs. fractional), and rheology of the magma reservoir (isobaric vs. isochoric vs. transitional). We run simulations through as much of the crystallization interval as possible, but focus on the first ~50 wt. % crystallization, most relevant for volcanic systems. In all simulations, we observe near-invariant behavior when the system becomes saturated in quartz, two feldspars and a fluid phase, from which point crystallization is essentially isothermal. Prior to the near-invariant, crystallization leads to gradual changes in bulk properties (e.g., < 1% volume decrease over 50 °C), which effectively results in modest pressure changes within the magma body (i.e., ~10 MPa). Upon reaching the near-invariant, the bulk properties change abruptly (e.g., > 5% volume increase in 0.1 °C), causing significant overpressurization of the magma body. The magnitude of this overpressurization (i.e. 10s to 100s of MPa depending on system conditions) is sufficient to

  11. Donor-site giant cell reaction following backfill with synthetic bone material during osteochondral plug transfer.

    PubMed

    Fowler, Donald E; Hart, Joseph M; Hart, Jennifer A; Miller, Mark D

    2009-10-01

    Osteochondral defects are common in younger, active patients. Multiple strategies have been used to treat these lesions, including microfracture and osteochondral plug transfer. We describe a patient experiencing chronic knee pain and a full-thickness cartilage defect on the lateral femoral condyle. After failing conservative management and microfracture surgery, the patient underwent osteochondral autograft plug transfer, with backfilling of the donor sites using synthetic bone graft substitute. Initial recovery was uncomplicated until the patient experienced pain following a twist of the knee. Magnetic resonance imaging for the subsequent knee injury revealed poor healing at the donor sites. The donor sites were debrided, and specimens revealed a foreign body giant cell reaction. Donor-site morbidity is of primary concern during osteochondral plug transfer; however, insufficient data exist to support the use of synthetic bone graft material. Our results indicate that off-label use of synthetic bone graft substitute during a primary procedure requires further investigation.

  12. Idiopathic giant cell myocarditis--a distinctive clinico-pathological entity.

    PubMed Central

    Davies, M J; Pomerance, A; Teare, R D

    1975-01-01

    Eleven cases of idiopathic giant cell myocarditis are described, The pathological features are unmistakable with serpiginous areas of myocardial necrosis, at the margins of which giant cells can be seen on histological examination. The aetiology of the condition remains obscure but associated pathology suggests that altered immunity may be a factor. The rapid clinical course is, however, highly suggestive of an infective cause though none has been found. Images PMID:1122272

  13. Giant cell tumor of the flexor hallucis longus tendon sheath: a case study.

    PubMed

    Findling, Jeff; Lascola, Natalie K; Groner, Thomas W

    2011-01-01

    Giant cell tumor of tendon sheath is infrequently documented in the foot and even less near the ankle. This case report involves such a tumor of the flexor hallucis longus tendon presenting at the posterior ankle. Diagnosis was aided by magnetic resonance imaging, and treatment consisted of complete surgical excision. Pathologic examination verified the diagnosis of giant cell tumor of tendon sheath, and follow-up magnetic resonance imaging revealed no remnants or recurrence of tumor 1 year after surgery.

  14. The prognostic significance of histomorphometry and immunohistochemistry in giant cell tumors of bone.

    PubMed

    Fornasier, V L; Protzner, K; Zhang, I; Mason, L

    1996-08-01

    Eighty-two cases of giant cell tumor (GCT) were reviewed. Hematoxylin-eosin-and hematoxylin, phloxine, saffron, and alcian green-stained sections (82 cases) were examined for mitotic rate, the number of giant cells, and the pleomorphism of the stromal cells. In 29 cases, the tumor was stained for CD68, alpha 1-antichymotrypsin (AIACT), S100 protein, Muramidase, and von Willebrand factor (factor VIII). The staining properties of mononuclear and multinucleated giant cells were compared. Morphometric analysis was performed on 14 cases with a LECO 2001 computer-assisted image analyzer (LECO Instruments Ltd, Mississauga, Ontario, Canada) and included absolute cell count, nuclear area, perimeter, roughness, roundness, and aspect and nuclear versus cytoplasmic ratios, measured both in the stromal cells and giant cells. The cases were divided into four groups: (1) cases with metastasis, (2) cases with recurrence, (3) cases with both metastasis and recurrence, and (4) cases with neither metastasis nor recurrence. Immunohistochemistry revealed a stronger AIACT than muramidase positivity in general. The staining was stronger in stromal cells than in giant cells. Giant cells in all tumors were positive for CD68. Stromal cells showed weaker positivity for the same stain. The number of asymmetrical mitotic figures was significantly greater in group 3 than in group 4 (P < .05). Morphometric assessment has identified a statistically significant difference in the aspect ratio and the roundness of the nuclei between these two groups. The other parameters did not differ significantly. In this article, the significance of these findings in prognostication and the histogenesis of the giant cell tumor are discussed. Their clinical applicability is yet to be determined.

  15. Multinucleated Giant Cancer Cells Produced in Response to Ionizing Radiation Retain Viability and Replicate Their Genome

    PubMed Central

    Mirzayans, Razmik; Andrais, Bonnie; Scott, April; Wang, Ying W.; Kumar, Piyush; Murray, David

    2017-01-01

    Loss of wild-type p53 function is widely accepted to be permissive for the development of multinucleated giant cells. However, whether therapy-induced multinucleation is associated with cancer cell death or survival remains controversial. Herein, we demonstrate that exposure of p53-deficient or p21WAF1 (p21)-deficient solid tumor-derived cell lines to ionizing radiation (between 2 and 8 Gy) results in the development of multinucleated giant cells that remain adherent to the culture dish for long times post-irradiation. Somewhat surprisingly, single-cell observations revealed that virtually all multinucleated giant cells that remain adherent for the duration of the experiments (up to three weeks post-irradiation) retain viability and metabolize 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), and the majority (>60%) exhibit DNA synthesis. We further report that treatment of multinucleated giant cells with pharmacological activators of apoptosis (e.g., sodium salicylate) triggers their demise. Our observations reinforce the notion that radiation-induced multinucleation may reflect a survival mechanism for p53/p21-deficient cancer cells. With respect to evaluating radiosensitivity, our observations underscore the importance of single-cell experimental approaches (e.g., single-cell MTT) as the creation of viable multinucleated giant cells complicates the interpretation of the experimental data obtained by commonly-used multi-well plate colorimetric assays. PMID:28208747

  16. Vertebrobasilar Infarction Related to Giant Cell (Temporal) Arteritis: Case Report

    PubMed Central

    HAISA, Toshihiko; TSUDA, Tokutaro; HAGIWARA, Kiyofumi; KIKUCHI, Takeshi; SEKI, Kunihiko

    2015-01-01

    An 84-year-old male with a 3-month history of headache and elevated C-reactive protein levels was admitted for biopsy of the superficial temporal artery, which led to the diagnosis of giant cell arteritis (GCA). Two days after prednisolone therapy was initiated, the patient began to experience transient vertigo attacks. Two days later, dysarthria, left-sided hemiparesis, right abducens palsy, and horizontal nystagmus developed. Magnetic resonance (MR) imaging disclosed fresh infarctions in the vertebrobasilar territory. Since the patient became drowsy because of brainstem compression and hydrocephalus due to cerebellar swelling, emergency suboccipital decompression surgery and ventricular drainage were performed. Subsequently, the patient’s consciousness levels improved. MR angiography revealed right vertebral artery (VA) occlusion and left VA stenosis due to arteritis. Ischemic stroke is a serious though relatively rare complication of GCA. Similar cases have been reported, in which ischemic stroke developed despite or possibly due to steroid therapy. To our knowledge, this is the first description of vertebrobasilar infarction associated with GCA in the Japanese population. The merits and potential demerits of steroid therapy are briefly discussed. PMID:24390182

  17. Vertebrobasilar infarction related to giant cell (temporal) arteritis: case report.

    PubMed

    Haisa, Toshihiko; Tsuda, Tokutaro; Hagiwara, Kiyofumi; Kikuchi, Takeshi; Seki, Kunihiko

    2015-01-01

    An 84-year-old male with a 3-month history of headache and elevated C-reactive protein levels was admitted for biopsy of the superficial temporal artery, which led to the diagnosis of giant cell arteritis (GCA). Two days after prednisolone therapy was initiated, the patient began to experience transient vertigo attacks. Two days later, dysarthria, left-sided hemiparesis, right abducens palsy, and horizontal nystagmus developed. Magnetic resonance (MR) imaging disclosed fresh infarctions in the vertebrobasilar territory. Since the patient became drowsy because of brainstem compression and hydrocephalus due to cerebellar swelling, emergency suboccipital decompression surgery and ventricular drainage were performed. Subsequently, the patient's consciousness levels improved. MR angiography revealed right vertebral artery (VA) occlusion and left VA stenosis due to arteritis. Ischemic stroke is a serious though relatively rare complication of GCA. Similar cases have been reported, in which ischemic stroke developed despite or possibly due to steroid therapy. To our knowledge, this is the first description of vertebrobasilar infarction associated with GCA in the Japanese population. The merits and potential demerits of steroid therapy are briefly discussed.

  18. Giant cell arteritis and polymyalgia rheumatica: current challenges and opportunities.

    PubMed

    Dejaco, Christian; Brouwer, Elisabeth; Mason, Justin C; Buttgereit, Frank; Matteson, Eric L; Dasgupta, Bhaskar

    2017-10-01

    The fields of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) have advanced rapidly, resulting in a new understanding of these diseases. Fast-track strategies and improved awareness programmes that prevent irreversible sight loss through early diagnosis and treatment are a notable advance. Ultrasonography and other imaging techniques have been introduced into routine clinical practice and there have been promising reports on the efficacy of biologic agents, particularly IL-6 antagonists such as tocilizumab, in treating these conditions. Along with these developments, which should improve outcomes in patients with GCA and PMR, new questions and unmet needs have emerged; future research should address which pathogenetic mechanisms contribute to the different phases and clinical phenotypes of GCA, what role imaging has in the early diagnosis and monitoring of GCA and PMR, and in which patients and phases of these diseases novel biologic drugs should be used. This article discusses the implications of recent developments in our understanding of GCA and PMR, as well as the unmet needs concerning epidemiology, pathogenesis, imaging and treatment of these diseases.

  19. The Effect of Diabetes Mellitus on Giant Cell Arteritis

    PubMed Central

    Abel, Anne S; Yashkin, Arseniy P; Sloan, Frank A; Lee, Michael S

    2015-01-01

    Objective To determine if type 2 diabetes mellitus (DM) is protective against giant cell arteritis (GCA) and to estimate the incidence of GCA diagnosis in the Medicare population. Methods Medicare 5% claims files from 1991-2011 were used to identify beneficiaries diagnosed with DM, but not GCA, within a three-year ascertainment period. Propensity score matching was used to define a control group of non-diabetics with comparable demographic covariates. Competing-risk regression was then used to assess the impact of DM diagnosis on GCA diagnosis. To allow for a three-year ascertainment period, the analysis sample was limited to beneficiaries over 68 years old at baseline. Results A total of 151,041 beneficiaries diagnosed with DM were matched to an equal number of controls. Mean study follow-up was 67.75 months. GCA was diagnosed among 1,116 beneficiaries with DM (0.73%) versus 465 (0.30%) controls. The risk of receiving a GCA diagnosis among patients with DM was increased by 100% (sub hazard ratio (SHR): 2.00; 95% confidence interval (CI): 1.78 2.25). The annual incidence of GCA diagnosis among U.S. Medicare beneficiaries over 68 was 93 in 100,000. Conclusion A DM diagnosis is not protective against a GCA diagnosis in the Medicare population. Our data suggests that a DM diagnosis increases the risk of GCA diagnosis within 5.7 years for Medicare beneficiaries over 68. PMID:25602744

  20. Cryosurgery as Additional Treatment in Tenosynovial Giant Cell Tumors

    PubMed Central

    Scholte, A.; van der Geest, I. C. M.; Hannink, G.; Schreuder, H. W. B.

    2016-01-01

    Introduction. Tenosynovial giant cell tumors (TGCT) emerge from the synovium and can behave aggressively. Surgical resection is the standard treatment. However, up to half of the patients with diffuse type show recurrences. Several additional treatments have been applied to reduce recurrences; none of these treatments was proven to be superior to surgical resection solely. This article describes the results of additional cryosurgery to surgical resection. Materials and Methods. We retrospectively evaluated 141 TGCT patients, between 1999 and 2007. Twelve patients had additional cryosurgery. The knee (n = 8), hip (n = 2), ankle (n = 1), and elbow (n = 1) were affected. Primary outcome variables were treatment indications, recurrences, and complications. Results. Indications for additional cryosurgery were extended disease, bone involvement, and locations that are difficult to surgically get disease-free such as cruciate ligaments. Five patients had recurrent disease, all of which had prior treatments. None of the primary treated patients had recurrent disease. One patient had a deep infection. Discussion. Cryosurgery may serve as an additional treatment for diffuse TCGT in selected cases. However, because of the small number of patients and the heterogeneous group we could not prove an advantage of additional cryosurgery over surgical resection only. Cryosurgery should be considered for further evaluation in a prospective study. If there is any effect it would be helpful, especially in patients with multiple TGCT recurrences. PMID:28115910

  1. Giant peritoneal loose body in the pelvic cavity confirmed by laparoscopic exploration: a case report and review of the literature.

    PubMed

    Zhang, Hong; Ling, Yun-zhi; Cui, Ming-ming; Xia, Zhi-xiu; Feng, Yong; Chen, Chun-sheng

    2015-03-24

    A 51-year-old previously healthy male underwent a routine medical examination. Computed tomography and ultrasonography showed an oval-shaped mass that was about 50 × 40 mm in size in the left iliac fossa. Prior to surgery, the lesion was suspected to be a teratoma with core calcification or stromal tumor derived from the rectosigmoid colon. During the procedure, a yellow-white, egg-shaped mass was discovered that was completely free from the pelvic cavity in front of the rectum. The giant, peritoneal loose body was taken out through the enlarged port site. Histological examination showed that the mass consisted of well-circumscribed, unencapsulated, paucicellular tissue, with an obviously hyalinized fibrosclerotic center. A giant peritoneal body is extremely rare. We report such a case and review previously published literature.

  2. Disappearance of giant cells and presence of newly formed bone in the pulmonary metastasis of a sacral giant-cell tumor following denosumab treatment: A case report.

    PubMed

    Yamagishi, Tetsuro; Kawashima, Hiroyuki; Ogose, Akira; Sasaki, Taro; Hotta, Tetsuo; Inagawa, Shoichi; Umezu, Hajime; Endo, Naoto

    2016-01-01

    A giant-cell tumor of the bone (GCTB) is a benign but locally aggressive bone tumor. Recently, the receptor activator of nuclear factor κB (RANK) ligand inhibitor, denosumab, has demonstrated activity against giant-cell tumors. The current study reports a case of a sacral GCTB with lung metastasis. A 19-year-old male patient presented with right buttock pain and right lower leg pain, and a sacral GCTB was diagnosed based on the histological analysis of a biopsy specimen. The patient was successfully treated with neoadjuvant denosumab therapy, which allowed curettage. In addition, the pulmonary nodule reduced in size following denosumab administration, and surgical resection was performed. Since the operation, the patient has been managed with the continued use of denosumab with no sign of recurrence. Microscopic findings from the surgical specimen following denosumab treatment revealed that the giant cells had disappeared and woven bone had formed. The specimen from the pulmonary nodule exhibited similar findings to the surgical specimen. It was reported that denosumab treatment was able to reduce the number of giant cells and RANK-positive stromal cells, and cause the formation of new bone in the primary lesion. The present study reports the first case to demonstrate the efficiency of denosumab in treating pulmonary metastasis of GCTB.

  3. Incidence Trends in the Diagnosis of Giant Cell Tumor of Bone in Sweden Since 1958.

    PubMed

    Rockberg, Julia; Bach, Bruce A; Amelio, Justyna; Hernandez, Rohini K; Sobocki, Patrik; Engellau, Jacob; Bauer, Henrik C F; Liede, Alexander

    2015-11-04

    The Swedish Cancer Registry (founded in 1958) constitutes a unique resource for epidemiological studies of giant cell tumor of bone with potential for use for population-based studies of incidence over time. The aim of this study was to provide what we believe is the first modern population-based assessment of the incidence trends of giant cell tumor, a unique osteoclastogenic lytic stromal tumor with both benign and malignant histological forms, and to compare the findings with data from the same registry on osteosarcoma, a tumor that may display similar histological characteristics. Cases were identified with use of codes for pathological bone tumor (International Classification of Diseases [ICD]-7 196). Specific morphological coding distinguishes benign (PAD 741) from malignant giant cell tumor (PAD 746) and osteosarcoma (PAD 766). During the period of 1958 to 2011, 4625 bone tumors were reported, including 505 giant cell tumors (383 benign and 122 malignant) and 1152 osteosarcomas. From 1958 to 1982 the ratio of malignant to benign giant cell tumors was 1.3, whereas from 1983 to 2011 the ratio inverted to 0.09, suggesting a change in the reporting or diagnosis of malignant or benign cases. Cases of giant cell tumor diagnosed from 1983 to 2011 displayed an age and sex distribution (median age at diagnosis, 34.0 years; 54% female) that were consistent with those in large published case series but differed from those in 1958 to 1982 (median age at diagnosis, 31.5 years; 48% female). The most current data (1983 to 2011) showed the giant cell tumor incidence in Sweden to be 1.3 per million per year, while the osteosarcoma incidence was 2.3 per million per year. Early Swedish Cancer Registry data (1958 to 1982) revealed a higher proportion of malignant giant cell tumors than seen in large sequential case series and a distinct age and sex profile compared with more recent data (1983 to 2011). This likely represents changes in the diagnostic workup and introduction of

  4. The Bishop Tuff giant magma body: An alternative to the Standard Model

    NASA Astrophysics Data System (ADS)

    Gualda, G. A.; Ghiorso, M. S.

    2012-12-01

    The Bishop Tuff (California), which erupted at 760 ka and formed the Long Valley caldera, is the archetypical example of a thermally and compositionally stably stratified giant magma body. The deposit includes only high-silica rhyolite, but it is zoned with an early-erupted, pyroxene-free, crystal-poor (5-20 wt. % crystals) lower unit (EBT) and a late-erupted, pyroxene-bearing, more crystal-rich (5-30 wt. % crystals) upper unit (LBT). Gradients in composition and temperature within the magma body were first inferred by Hildreth (1979): Fe-Ti oxide thermometry reveals a gradient in pre-eruptive temperatures from EBT to LBT, suggesting thermal stratification; and the homogeneity of phenocryst compositions within each pumice clast suggests stable compositional stratification. This view of the Bishop magma body - the Standard Model - has remained largely unchallenged by subsequent work; we present new pre-eruptive temperature (T) and pressure (P) estimates to critically assess its viability. The pinnacle of the Standard Model is the gradient in pre-eruptive T and fO2 inferred from Fe-Ti oxides. Fe-Ti oxides also constrain TiO2 activity in the melt (Ghiorso & Gualda, CMP, in press); the positive correlation between T and aTiO2 observed in the Bishop dataset cannot be explained by magmatic crystallization, and comparison with aTiO2 from rhyolite-MELTS shows that Fe-Ti oxides were not in equilibrium with melt and do not record pre-eruptive conditions. We use zircon saturation temperatures calculated with literature glass inclusion data (Wallace et al., JGR, 1999; Anderson et al., JPet, 2000) to assess pre-eruptive temperatures; Zr contents in glass inclusions vary over a narrow interval (~70-110 ppm) for both EBT and LBT, yielding T between 720 and 755 °C for both, arguing against the inferred thermal stratification. Geobarometry should yield systematic differences between EBT and LBT. Published H2O-CO2 glass inclusion data yield overlapping P for EBT and LBT pumice

  5. Giant cell glioblastoma in the cerebrum of a Pembroke Welsh corgi.

    PubMed

    Giri, D K; Aloisio, F; Alosio, F; Ajithdoss, D K; Ambrus, A; Lidbury, J A; Hein, H E; Porter, B F

    2011-05-01

    A 6-year-old, neutered female Pembroke Welsh corgi was presented with a 1-month history of ataxia and panting. The clinical signs progressed until the dog became anorexic, obtunded and exhibited circling to the left. At necropsy examination, a mass was detected in the left forebrain, impinging on the cribriform plate. Microscopically, the mass was composed of sheets of round to pleomorphic neoplastic cells with vacuolated cytoplasm. Nuclear atypia, anisocytosis and anisokaryosis were common. Numerous bizarre, multinucleated giant cells containing 60 or more nuclei and giant mononuclear cells were present. The matrix contained abundant reticulin. Immunohistochemistry revealed the neoplastic cells uniformly to express vimentin, and a small number of neoplastic cells expressed glial fibrillary acid protein. A diagnosis of giant cell glioblastoma was made. Although well recognized in man, this tumour has been documented rarely in the veterinary literature.

  6. The hyperpolarization-activated non-specific cation current (In ) adjusts the membrane properties, excitability, and activity pattern of the giant cells in the rat dorsal cochlear nucleus.

    PubMed

    Rusznák, Zoltán; Pál, Balázs; Kőszeghy, Aron; Fu, Yuhong; Szücs, Géza; Paxinos, George

    2013-03-01

    Giant cells of the cochlear nucleus are thought to integrate multimodal sensory inputs and participate in monaural sound source localization. Our aim was to explore the significance of a hyperpolarization-activated current in determining the activity of giant neurones in slices prepared from 10 to 14-day-old rats. When subjected to hyperpolarizing stimuli, giant cells produced a 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyridinium chloride (ZD7288)-sensitive inward current with a reversal potential and half-activation voltage of -36 and -88 mV, respectively. Consequently, the current was identified as the hyperpolarization-activated non-specific cationic current (Ih ). At the resting membrane potential, 3.5% of the maximum Ih conductance was available. Immunohistochemistry experiments suggested that hyperpolarization-activated, cyclic nucleotide-gated, cation non-selective (HCN)1, HCN2, and HCN4 subunits contribute to the assembly of the functional channels. Inhibition of Ih hyperpolarized the membrane by 6 mV and impeded spontaneous firing. The frequencies of spontaneous inhibitory and excitatory postsynaptic currents reaching the giant cell bodies were reduced but no significant change was observed when evoked postsynaptic currents were recorded. Giant cells are affected by biphasic postsynaptic currents consisting of an excitatory and a subsequent inhibitory component. Inhibition of Ih reduced the frequency of these biphasic events by 65% and increased the decay time constants of the inhibitory component. We conclude that Ih adjusts the resting membrane potential, contributes to spontaneous action potential firing, and may participate in the dendritic integration of the synaptic inputs of the giant neurones. Because its amplitude was higher in young than in adult rats, Ih of the giant cells may be especially important during the postnatal maturation of the auditory system.

  7. Treatment and outcome of giant cell tumors of the pelvis

    PubMed Central

    2009-01-01

    Background and purpose Giant cell tumors (GCTs) of bone rarely affect the pelvis. We report on 20 cases that have been treated at our institution during the last 20 years. Methods 20 patients with histologically benign GCT of the pelvis were included in this study. 9 tumors were primarily located in the iliosacral area, 6 in the acetabular area, and 5 in the ischiopubic area. 8 patients were treated by intralesional curettage and 6 by intralesional resection with additional curettage of the margins. 3 patients with iliacal tumors were treated by wide resection. 2 patients were treated by a combination of external beam irradiation and surgery, and 1 patient solely by irradiation. In addition, 9 patients received selective arterial embolization one day before surgery. Of the 6 patients with acetabular tumors, 1 secondarily received an endoprosthesis and 1 was primarily treated by hip transposition. The patients were followed for a median time of 3 (1–11) years. Results 1 patient with a pubic tumor developed a local recurrence 1 year after intralesional resection and additional curettage of the margins. The recurrence presented as a small soft tissue mass within the scar tissue of the gluteal muscles and was treated by resection. No secondary sarcoma was detected and none of the patients developed pulmonary metastases or multicentricity. No major complication occurred during surgery. Interpretation We conclude that most GCTs of the pelvis can be treated by intralesional procedures. For tumors of the iliac wing, wide resection can be an alternative. Surgical treatment of tumors affecting the acetabular region often results in functional impairment. Pre-surgical selective arterial embolization appears to be a safe procedure that may reduce the risk of local recurrence. PMID:19916695

  8. Radiological and Histopathological Outcome of Giant Cell Tumor of Femur with Denosumab Treatment: A Case Report.

    PubMed

    Menon, Preethi Dileep; Krishnakumar, R; Jojo, Annie

    2016-12-01

    Giant Cell Tumour of Bone (GCTB) is a benign but locally aggressive osteolytic skeletal neoplasm of young adults consisting of giant cells expressing RANK (Receptor Activator of Nuclear Factor-κB) and mesenchymal spindle-like stromal cells expressing RANKL (RANK ligand). The interaction of these cells leads to bone resorption. Recently, the RANKL inhibitor, denosumab, has demonstrated activity against giant-cell tumours. The current article reports a case of a Giant cell tumour of left distal femur with pathological fracture. A 34-year-old male patient presented with history of on and off dull aching pain in the left knee for 4 months followed by a history of trivial fall. He sustained a closed injury in the left knee, following which he was unable to bear weight and developed pain and swelling in left knee. Conventional radiographs and Computerized tomography (CT) was done which showed the presence of a left distal femoral osteolytic lesion and a histological analysis of a biopsy specimen confirmed the diagnosis of GCTB. The patient was treated with neoadjuvant denosumab therapy which resulted in successful downstaging of the tumour followed by extended curettage of the lesion with high speed burr and argon laser cautery. The post-curettage microscopic examination revealed the absence of osteoclast-type giant cells.

  9. Radiological and Histopathological Outcome of Giant Cell Tumor of Femur with Denosumab Treatment: A Case Report

    PubMed Central

    Krishnakumar, R.; Jojo, Annie

    2016-01-01

    Giant Cell Tumour of Bone (GCTB) is a benign but locally aggressive osteolytic skeletal neoplasm of young adults consisting of giant cells expressing RANK (Receptor Activator of Nuclear Factor-κB) and mesenchymal spindle-like stromal cells expressing RANKL (RANK ligand). The interaction of these cells leads to bone resorption. Recently, the RANKL inhibitor, denosumab, has demonstrated activity against giant-cell tumours. The current article reports a case of a Giant cell tumour of left distal femur with pathological fracture. A 34-year-old male patient presented with history of on and off dull aching pain in the left knee for 4 months followed by a history of trivial fall. He sustained a closed injury in the left knee, following which he was unable to bear weight and developed pain and swelling in left knee. Conventional radiographs and Computerized tomography (CT) was done which showed the presence of a left distal femoral osteolytic lesion and a histological analysis of a biopsy specimen confirmed the diagnosis of GCTB. The patient was treated with neoadjuvant denosumab therapy which resulted in successful downstaging of the tumour followed by extended curettage of the lesion with high speed burr and argon laser cautery. The post-curettage microscopic examination revealed the absence of osteoclast-type giant cells. PMID:28208958

  10. Diagnosing an atypical site of giant cell arteritis with magnetic resonance angiography: a case report.

    PubMed

    Tan, Boon L; Liu, Jonathan J; Yong, Tuck Y; Tan, Chrismin C; Li, Jordan Y

    2016-06-23

    Giant cell arteritis typically involves the temporal arteries, but can involve other cranial arteries. Temporal artery biopsy is the mainstay for the diagnosis of giant cell arteritis; however, biopsy may be problematic if giant cell arteritis involves other cranial arteries that are inaccessible for sampling. In these situations, magnetic resonance angiography is a useful, non-invasive adjunctive method in the diagnosis of giant cell arteritis. In this case report, we describe a case of giant cell arteritis involving only the occipital artery which was revealed by magnetic resonance angiography. A 67-year-old Caucasian man was admitted to our hospital with a 4-week history of malaise, fever, and mild occipital headaches. There were no other positive findings on physical examination. Laboratory studies were remarkable for normocytic anemia, raised inflammatory markers, and mildly deranged liver function tests. To exclude intracranial pathology, he underwent a cranial magnetic resonance imaging with gadolinium, which demonstrated a thickened wall and mural enhancement of his right occipital artery, consistent with giant cell arteritis. His temporal arteries were normal. His occipital arteries were not accessible for biopsy and he was commenced on high-dose prednisolone (60 mg daily). His symptoms resolved completely after a week of glucocorticoid steroid treatment and he was well on 5 mg of prednisolone once a day on follow-up. While magnetic resonance angiography may not replace the need for biopsy, it may have a diagnostic role in suspected giant cell arteritis, such as when the involved arteries are inaccessible for biopsy.

  11. Lipid Bodies in Inflammatory Cells

    PubMed Central

    Melo, Rossana C. N.; D’Avila, Heloisa; Wan, Hsiao-Ching; Bozza, Patrícia T.; Dvorak, Ann M.; Weller, Peter F.

    2011-01-01

    Lipid bodies (LBs), also known as lipid droplets, have increasingly been recognized as functionally active organelles linked to diverse biological functions and human diseases. These organelles are actively formed in vivo within cells from the immune system, such as macrophages, neutrophils, and eosinophils, in response to different inflammatory conditions and are sites for synthesis and storage of inflammatory mediators. In this review, the authors discuss structural and functional aspects of LBs and current imaging techniques to visualize these organelles in cells engaged in inflammatory processes, including infectious diseases. The dynamic morphological aspects of LBs in leukocytes as inducible, newly formable organelles, elicitable in response to stimuli that lead to cellular activation, contribute to the evolving understanding of LBs as organelles that are critical regulators of different inflammatory diseases, key markers of leukocyte activation, and attractive targets for novel anti-inflammatory therapies. PMID:21430261

  12. Linking genomic reorganization to tumor initiation via the giant cell cycle

    PubMed Central

    Niu, N; Zhang, J; Zhang, N; Mercado-Uribe, I; Tao, F; Han, Z; Pathak, S; Multani, A S; Kuang, J; Yao, J; Bast, R C; Sood, A K; Hung, M-C; Liu, J

    2016-01-01

    To investigate the mechanisms underlying our recent paradoxical finding that mitotically incapacitated and genomically unstable polyploid giant cancer cells (PGCCs) are capable of tumor initiation, we labeled ovarian cancer cells with α-tubulin fused to green fluorescent protein, histone-2B fused to red fluorescent protein and FUCCI (fluorescent ubiquitination cell cycle indicator), and tracked the spatial and time-dependent change in spindle and chromosomal dynamics of PGCCs using live-cell fluorescence time-lapse recording. We found that single-dose (500 nm) treatment with paclitaxel paradoxically initiated endoreplication to form PGCCs after massive cell death. The resulting PGCCs continued self-renewal via endoreplication and further divided by nuclear budding or fragmentation; the small daughter nuclei then acquired cytoplasm, split off from the giant mother cells and acquired competency in mitosis. FUCCI showed that PGCCs divided via truncated endoreplication cell cycle (endocycle or endomitosis). Confocal microscopy showed that PGCCs had pronounced nuclear fragmentation and lacked expression of key mitotic proteins. PGCC-derived daughter cells were capable of long-term proliferation and acquired numerous new genome/chromosome alterations demonstrated by spectral karyotyping. These data prompt us to conceptualize a giant cell cycle composed of four distinct but overlapping phases, initiation, self-renewal, termination and stability. The giant cell cycle may represent a fundamental cellular mechanism to initiate genomic reorganization to generate new tumor-initiating cells in response to chemotherapy-induced stress and contributes to disease relapse. PMID:27991913

  13. Biophysical characterisation of electrofused giant HEK293-cells as a novel electrophysiological expression system

    SciTech Connect

    Zimmermann, D.; Terpitz, U.; Zhou, A.; Reuss, R.; Mueller, K.; Sukhorukov, V.L.; Gessner, P.; Nagel, G.; Zimmermann, U.; Bamberg, E. . E-mail: ernst.bamberg@mpibp-frankfurt.mpg.de

    2006-09-22

    Giant HEK293 cells of 30-65 {mu}m in diameter were produced by three-dimensional multi-cell electrofusion in 75 mOsm sorbitol media. These strong hypotonic conditions facilitated fusion because of the spherical shape and smooth membrane surface of the swollen cells. A regulatory volume decrease (RVD), as observed at higher osmolalities, did not occur at 75 mOsm. In contrast to field-treated, but unfused cells, the increase in volume induced by hypotonic shock was only partly reversible in the case of fused giant cells after their transfer into isotonic medium. The large size of the electrofused cells allowed the study of their electrophysiological properties by application of both whole-cell and giant excised patch-clamp techniques. Recordings on giant cells yielded a value of 1.1 {+-} 0.1 {mu}F/cm{sup 2} for the area-specific membrane capacitance. This value was consistent with that of the parental cells. The area-specific conductivity of giant cells (diameter > 50 {mu}m) was found to be between 12.8 and 16.1 {mu}S/cm{sup 2}, which is in the range of that of the parental cells. Measurements with patch-pipettes containing fluorescein showed uniform dye uptake in the whole-cell configuration, but not in the cell-attached configuration. The diffusion-controlled uniform uptake of the dye into the cell interior excludes internal compartmentalisation. The finding of a homogeneous fusion was also supported by expression of the yellow fluorescent protein YFP (as part of the fusion-protein ChR2-YFP) in giant cells since no plasma-membrane bound YFP-mediated fluorescence was detected in the interior of the electrofused cells. Functional expression and the electrophysiological characterisation of the light-activated cation channel Channelrhodopsin 2 (ChR2) yielded similar results as for parental cells. Most importantly, the giant cells exhibited a comparable expression density of the channel protein in the plasma membrane as observed in parental cells. This demonstrates that

  14. Respiration characteristics of mitochondria in parental and giant transformed cells of the murine Nemeth-Kellner lymphoma.

    PubMed

    Horbay, Rostyslav O; Manko, Bohdan O; Manko, Volodymyr V; Lootsik, Maxim D; Stoika, Rostyslav S

    2012-01-01

    Respiration characteristics of mitochondria of the parental and giant cells of murine NK/Ly (Nemeth-Kellner lymphoma) were studied. The giant cell-enriched ascites were obtained by serial intraperitoneal injections of vinblastine in tumour-bearing mice. Ascites containing >70% giant cells were used. Their diameter of was over 17 μm (~2800 μm(3)), while the diameter of the parental cells was 12.7 μm (1100 μm(3)). The respiration rate of mitochondria in situ was measured by oxygen consumption in intact and digitonin-permeabilized NK/Ly cells. Endogenous respiration of intact giant NK/Ly cells was three times higher compared to the parental ones, roughly in agreement with the volume change. The giant NK/Ly cells were far more resistant to permeabilization with digitonin than the parental cells, as shown by Trypan Blue and LDH (lactate dehydrogenase) release tests. After digitonin permeabilization, oxygen consumption was reduced to a minimal level (0.06 ng atom O/(s × 106 cells) in both types of cells. Addition of α-ketoglutarate or succinate to the incubation medium increased oxygen consumption in the parental cells by 46 and 164% respectively. In the giant NK/Ly cells, the corresponding increases were 164 and 276%. Addition of ADP to α-ketoglutarate- or succinate-supplemented medium further stimulated oxygen consumption of the permeabilized NK/Ly cells; however, the effect of ADP was more pronounced in the giant cells. In addition, indices of respiratory control were significantly higher in the giant cells. Oligomycin suppressed considerably the respiration of the intact giant cells but had a much weaker effect on parental cells. Thus, giant NK/Ly cells possess much higher respiration rates and show tighter coupling between the respiration and oxidative phosphorylation compared with parental cells. © The Author(s) Journal compilation © 2012 Portland Press Limited

  15. Structure and Evolution of Giant Cells in Global Models of Solar Convection

    NASA Astrophysics Data System (ADS)

    Miesch, Mark S.; Brun, Allan Sacha; DeRosa, Marc L.; Toomre, Juri

    2008-01-01

    The global scales of solar convection are studied through three-dimensional simulations of compressible convection carried out in spherical shells of rotating fluid that extend from the base of the convection zone to within 15 Mm of the photosphere. Such modeling at the highest spatial resolution to date allows study of distinctly turbulent convection, revealing that coherent downflow structures associated with giant cells continue to play a significant role in maintaining the differential rotation that is achieved. These giant cells at lower latitudes exhibit prograde propagation relative to the mean zonal flow, or differential rotation, that they establish, and retrograde propagation of more isotropic structures with vortical character at mid and high latitudes. The interstices of the downflow networks often possess strong and compact cyclonic flows. The evolving giant-cell downflow systems can be partly masked by the intense smaller scales of convection driven closer to the surface, yet they are likely to be detectable with the helioseismic probing that is now becoming available. Indeed, the meandering streams and varying cellular subsurface flows revealed by helioseismology must be sampling contributions from the giant cells, yet it is difficult to separate out these signals from those attributed to the faster horizontal flows of supergranulation. To aid in such detection, we use our simulations to describe how the properties of giant cells may be expected to vary with depth and how their patterns evolve in time.

  16. Giant cytoplasmic granules in Langerhans cells of Chediak-Higashi syndrome.

    PubMed

    Carrillo-Farga, J; Gutiérrez-Palomera, G; Ruiz-Maldonado, R; Rondán, A; Antuna, S

    1990-02-01

    Giant membrane-bound cytoplasmic granules were found in the epidermal Langerhans cells of a patient with the Chediak-Higashi syndrome. These cells also contained normal-appearing Birbeck granules. The giant granules had a granular or sometimes globular internal structure; they are believed to derive from fusion of lysosomes or some portion of Birbeck granules. It is unclear whether this morphologic change in Langerhans cell interferes with their antigen-presenting function; it may be, in part, responsible for the frequent infections seen in patients with Chediak-Higashi syndrome that are otherwise more clearly related to the abnormalities in neutrophils and lymphocytes. The Langerhans cell is another cellular type in Chediak-Higashi syndrome in which giant cytoplasmic granules are found.

  17. Eukaryotic cells and their cell bodies: Cell Theory revised.

    PubMed

    Baluska, Frantisek; Volkmann, Dieter; Barlow, Peter W

    2004-07-01

    Cell Theory, also known as cell doctrine, states that all eukaryotic organisms are composed of cells, and that cells are the smallest independent units of life. This Cell Theory has been influential in shaping the biological sciences ever since, in 1838/1839, the botanist Matthias Schleiden and the zoologist Theodore Schwann stated the principle that cells represent the elements from which all plant and animal tissues are constructed. Some 20 years later, in a famous aphorism Omnis cellula e cellula, Rudolf Virchow annunciated that all cells arise only from pre-existing cells. General acceptance of Cell Theory was finally possible only when the cellular nature of brain tissues was confirmed at the end of the 20th century. Cell Theory then rapidly turned into a more dogmatic cell doctrine, and in this form survives up to the present day. In its current version, however, the generalized Cell Theory developed for both animals and plants is unable to accommodate the supracellular nature of higher plants, which is founded upon a super-symplasm of interconnected cells into which is woven apoplasm, symplasm and super-apoplasm. Furthermore, there are numerous examples of multinucleate coenocytes and syncytia found throughout the eukaryote superkingdom posing serious problems for the current version of Cell Theory. To cope with these problems, we here review data which conform to the original proposal of Daniel Mazia that the eukaryotic cell is composed of an elemental Cell Body whose structure is smaller than the cell and which is endowed with all the basic attributes of a living entity. A complement to the Cell Body is the Cell Periphery Apparatus, which consists of the plasma membrane associated with other periphery structures. Importantly, boundary structures of the Cell Periphery Apparatus, although capable of some self-assembly, are largely produced and maintained by Cell Body activities and can be produced from it de novo. These boundary structures serve not only as

  18. Treatment with Doxycycline of Generalized Annular Elastolytic Giant Cell Granuloma Associated with Borrelia burgdorferi Infection

    PubMed Central

    Tas, B; Caglar, A; Ozdemir, B

    2015-01-01

    ABSTRACT This is a case of generalized annular elastolytic giant cell granuloma (AEGCG) associated with borrelia infection and genes of p-30, p-31, p-39. A possible cross-mediated reaction from the T-cell type which might have induced the AEGCG is discussed from the concept of “heat-shock proteins (HSPs) and molecular mimicry”. PMID:26624605

  19. Varicella zoster virus in the temporal artery of a patient with giant cell arteritis.

    PubMed

    Nagel, Maria A; Khmeleva, Nelly; Boyer, Philip J; Choe, Alexander; Bert, Robert; Gilden, Don

    2013-12-15

    We recently detected varicella zoster virus (VZV) in the temporal arteries (TA) of 5/24 patients with clinically suspect giant cell arteritis (GCA) whose TAs were GCA-negative pathologically; in those GCA-negative, VZV+TAs, virus antigen predominated in the arterial adventitia, but without medial necrosis and multinucleated giant cells. During our continuing search for VZV antigen in GCA-negative TAs, in the TA of one subject, we found abundant VZV antigen, as well as VZV DNA, in multiple regions (skip areas) of the TA spanning 350 μm, as well as in skeletal muscle adjacent to the infected TA. Additional pathological analysis of sections adjacent to those containing viral antigen revealed inflammation involving the arterial media and abundant multinucleated giant cells characteristic of GCA. Detection of VZV in areas of the TA with pathological features of GCA warrants further correlative pathological-virological analysis of VZV in GCA. © 2013.

  20. Giant Cell Lesions in Noonan Syndrome: Case Report and Review of The Literature

    PubMed Central

    Bufalino, Andreia; Carrera, Manoela; Carlos, Roman

    2010-01-01

    Noonan-like/multiple giant cell lesion syndrome (NS/MGCLS) is a rare condition with phenotypic overlap with Noonan syndrome (NS). Once thought to be a specific and separate entity, it is now suggested to be a variant of the NS spectrum. We report a patient with classical cardinal features of NS, including short stature, mild ptosis, hypertelorism, down-slating palpebral fissures, low-set and posteriorly angulated ears, short neck, pectus excavatum, widely spaced nipples and cryptochidism, which were associated with bilateral central giant cell lesions in the mandible and germ-line mutation (C218T, Thr73Ile) in the exon 3 of the PTPN11 gene. The similar clinical and genetic aspects support the observation that NS/MGCLS is a variant of NS and giant cell lesions are an integrant part of this disorder. PMID:20383758

  1. Treatment of central giant cell lesions using bisphosphonates with intralesional corticosteroid injections

    PubMed Central

    2012-01-01

    Central giant cell lesions are benign intraosseous proliferative lesions that have considerable local aggressiveness. Nonsurgical treatment methods, such as intralesional corticosteroid injections, systemic calcitonin and interferon have been reported. Recently, bisphosphonates have been used to treat central giant cell lesions. A case of a 36-year-old male with a central giant cell lesion crossing the mandibular midline was treated with intralesional corticosteroids combined with alendronate sodium for the control of systemic bone resorption. The steroid injections and the use of bisphosphonates were stopped after seven months when further needle penetration into the lesion was not possible due to new bone formation. After two years, the bony architecture was near normal, and only minimal radiolucency was present around the root apices of the involved teeth. The patient was followed up for four years, and panoramic radiography showed areas of new bone formation. Thus far, neither recurrence nor side effects of the medication have been detected. PMID:22913518

  2. Giant cell granuloma of the maxilla. Global management, review of literature and case report

    PubMed Central

    Manzano-Solo de Zaldívar, Damián; González-García, Raúl; Ruíz-Laza, Luís; Villanueva-Alcojol, Laura; González-Ballester, David; Hernández Vila, Cristina; Monje-Gil, Florencio

    2012-01-01

    Giant cell granuloma is a relatively rare benign entity but can be locally aggressive. Histologically characterized by intense proliferation of multinucleated giant cells and fibroblasts. Affects bone supported tissues. Definitive diagnosis is given by biopsy. Clinically manifest as a mass or nodule of reddish color and fleshy, occasionally ulcerated surface. They can range from asymptomatic to destructive lesions that grow quickly. It is a lesion to be considered in the differential diagnosis of osteolytic lesions affecting the maxilla or jaw. Its management passed from conservative treatment with intralesional infiltration of corticosteroids, calcitonin or interferon, to the surgical resection and reconstruction, for example with microvascular free flaps. Key words:Giant cell granuloma, intralesional injection, microvascular free flap, fibula. PMID:24558538

  3. The suitability of the ultrasound biomicroscope for establishing texture in giant cell arteritis

    PubMed Central

    Roters, S.; Szurman, P.; Engels, B.; Brunner, R.

    2001-01-01

    AIM—To establish whether ultrasound biomicroscope (UBM) is a helpful tool in locating the arterial segment responsible in patients with segmental attacks in giant cell arteritis
METHODS—The superficial temporal arteries of 19 patients with suspected giant cell arteritis were examined with the UBM before biopsy.
RESULTS—20 specimens provided the histological proof of giant cell arteritis in five patients. Side differences, a dark perivascular halo, and high reflexivity of the intra-arterial space were found.
CONCLUSION—it is assumed that there are two types of arteritic inflammation: (1) the occlusion of intra-arterial space due to intimal fibrosis (UBM: high reflexive "filling"), and (2) inflammation of the perivascular zone with oedematous thickening and infiltration of the media (UBM: dark halo) and its combination. UBM is helpful in obtaining an indication of the side and segment for biopsy.

 PMID:11466252

  4. Everolimus Treatment for an Early Infantile Subependymal Giant Cell Astrocytoma With Tuberous Sclerosis Complex.

    PubMed

    Fukumura, Shinobu; Watanabe, Toshihide; Takayama, Rumiko; Minagawa, Kimio; Tsutsumi, Hiroyuki

    2015-08-01

    Subependymal giant cell astrocytomas are benign tumors often observed with tuberous sclerosis complex. These tumors are rarely diagnosed during fetal life or early infancy. Until recently, the only available treatment has been surgical resection. Current clinical research has demonstrated that everolimus can induce these tumors' regression. We report a 19-month-old boy with tuberous sclerosis complex. At 2 months of age, he presented with congenital subependymal giant cell astrocytoma that was complicated by refractory epilepsy and severe mental retardation. Treatment with everolimus was started when he was 10 months old. Three months after initiating everolimus, the tumor was significantly reduced in size, and the reduction was subsequently maintained. His seizures decreased and he showed cognitive and developmental improvement. No severe adverse events have been observed to date. Everolimus has promise as an effective alternative to surgery for subependymal giant cell astrocytomas during early infancy.

  5. Giant cell tumor of the greater wing of the sphenoid: an unusual presentation.

    PubMed

    Pelaz, Andrés Coca; Llorente Pendás, José L; Rodrigo Tapia, Juan P; Suárez Nieto, Carlos

    2008-05-01

    We report a very unusual presentation of giant cell tumor probably originated on the greater wing of the sphenoid and show a review about the knowledge and the treatment of the lesion in this rare localization. We treated a 48-year-old man with a giant cell tumor of the infratemporal fossa. He presented with a right-side hearing loss and facial pain. The tumor was resected by means of a subtemporal-preauricular approach, and after 12 months of follow-up, the patient is free of recurrence. Giant cell tumors of the skull base are an extremely rare neoplasm, and there is not much information on the literature about the treatment and the prognostic. Wide resection ought to be made, and at the follow-up, the clinician must try to diagnose not only local recurrence but also the possibility of distant metastases to the lung.

  6. Venous thrombosis in patients with giant cell arteritis: Features and outcomes in a cohort study.

    PubMed

    Ly, Kim Heang; Liozon, Eric; Dalmay, François; Gondran, Guillaume; Palat, Sylvain; Bézanahary, Holy; Lapébie, François-Xavier; Cypierre, Anne; Nadalon, Sylvie; Preux, Pierre-Marie; Fauchais, Anne-Laure

    2017-05-01

    To describe the features and outcomes of patients with giant cell arteritis who developed venous thrombosis. Inception cohort study including 428 newly diagnosed patients of giant cell arteritis from 1976 to 2014. Clinical and biological data and outcomes were analysed by comparing patients with and without venous thrombosis. Twenty-six patients (6%) developed venous thrombosis, 12 of whom presented with pulmonary embolism. The mean time between the onset of giant cell arteritis symptoms and venous thrombosis occurrence was 248.8±215.0 days. No difference was observed between the two groups in clinical or laboratory data collected at diagnosis. The mean time from the start of prednisone to venous thrombosis diagnosis was 187.7±217.0 days. The average dose of prednisone at venous thrombosis onset was 21.5mg/day. The venous thrombosis group had a higher number of glucocorticoid-related adverse effects (mean, 3.1 vs 1.1; P<0.0001), a higher mortality rate (58% vs 33%, P=0.01) and a higher proportion of deaths occurring during glucocorticoid treatment (31% vs 14%, P=0.03). Death was related to venous thrombosis in four patients. The occurrence of overt venous thrombosis is more than anecdotal among patients treated for giant cell arteritis. Venous thrombosis does not rely on the active phase of giant cell arteritis, but could be associated with long-term use of glucocorticoids. Because venous thrombosis may be associated with an increased mortality risk in patients with giant cell arteritis, a high index of suspicion should be applied in appropriate settings, especially in patients experiencing multiple glucocorticoid-related adverse effects. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  7. Nonaggressive central giant cell granuloma mimicking chronic inflammatory enlargement: a case report.

    PubMed

    Goyal, Lata; Gupta, Namita; Gupta, N D; Bey, Afshan

    2014-01-01

    This article presents a case of giant cell granuloma in a 24-year-old man. Clinical, histopathological, and radiographic findings are discussed and a differential diagnosis and treatment plan are suggested. Clinical behavior among lesions may vary between nonaggressive and aggressive forms, and even radiographic appearances are not identical. The present case resembled a variety of conditions clinically but was diagnosed histopathologically as giant cell granuloma. This case is presented to emphasize the importance of histopathologic examination to ensure proper diagnosis and treatment.

  8. Giant Cell Tumour of Proximal Phalanx of Ring Finger: Case Report and Review of Literature

    PubMed Central

    Soni, Rishit; Shah, Malkesh; Patel, Amit; Golwala, Paresh

    2016-01-01

    Giant cell tumour (GCT) of bone arising from a phalanx of a finger is extremely rare. Only two percent of all reported GCTs are found in the hand, which show a higher rate of recurrence as compared to those occurring at a more proximal location. Here we report a rare case of giant cell tumour of proximal phalanx of the ring finger in a 20-year-old male, which was treated with extended curettage and bone grafting. After two years of follow-up, the patient was asymptomatic with complete functional recovery and no signs of recurrence. PMID:27900230

  9. Coevolution of neoplastic epithelial cells and multilineage stroma via polyploid giant cells during immortalization and transformation of mullerian epithelial cells

    PubMed Central

    Zhang, Shiwu; Mercado-Uribe, Imelda; Sood, Anil; Bast, Robert C.; Liu, Jinsong

    2016-01-01

    Stromal cells are generally considered to be derived primarily from the host's normal mesenchymal stromal cells or bone marrow. However, the origins of stromal cells have been quite controversial. To determine the role of polyploidy in tumor development, we examined the fate of normal mullerian epithelial cells during the immortalization and transformation process by tracing the expression of SV40 large T antigen. Here we show that immortalized or HRAS-transformed mullerian epithelial cells contain a subpopulation of polyploid giant cells that grow as multicellular spheroids expressing hematopoietic markers in response to treatment with CoCl2. The immortalized or transformed epithelial cells can transdifferentiate into stromal cells when transplanted into nude mice. Immunofluorescent staining revealed expression of stem cell factors OCT4, Nanog, and SOX-2 in spheroid, whereas expression of embryonic stem cell marker SSEA1 was increased in HRAS-transformed cells compared with their immortalized isogenic counterparts. These results suggest that normal mullerian epithelial cells are intrinsically highly plastic, via the formation of polyploid giant cells and activation of embryonic stem-like program, which work together to promote the coevolution of neoplastic epithelial cells and multiple lineage stromal cells. PMID:27382431

  10. Mast cell tumour in a giant Galapagos tortoise (Geochelone nigra vicina).

    PubMed

    Santoro, M; Stacy, B A; Morales, J A; Gastezzi-Arias, P; Landazuli, S; Jacobson, E R

    2008-01-01

    A well-differentiated cutaneous mast cell tumour was diagnosed in a subadult female giant Galapagos tortoise. The tumour was a pedunculated, verrucose mass located near the base of the neck. The histological features, which were diagnostic for a mast cell tumour, included abundant intracytoplasmic granules that were stained metachromatically with Giemsa and toluidine blue stains. Mast cell tumours are rare in reptiles, and this is the first description of a mast cell tumour in a chelonian.

  11. Characteristics of mesenchymal stem cells isolated from bone marrow of giant panda.

    PubMed

    Liu, Yuliang; Liu, Yang; Yie, Shangmian; Lan, Jingchao; Pi, Jinkui; Zhang, Zhihe; Huang, He; Cai, Zhigang; Zhang, Ming; Cai, Kailai; Wang, Hairui; Hou, Rong

    2013-09-01

    In present study, we report on bone marrow (BM) mesenchymal stem cells (MSCs) that are isolated from giant pandas. Cells were collected from the BM of two stillborn giant pandas. The cells were cultured and expanded in 10% fetal bovine serum medium. Cell morphology was observed under an inverted microscopy, and the proliferation potential of the cells was evaluated by counting cell numbers for eight consecutive days. Differentiation potentials of the cells were determined by using a variety of differentiation protocols for osteocytes, adipocytes, neuron cells, and cardiomyocytes. Meanwhile, the specific gene expressions for MSCs or differentiated cells were analyzed by RT-PCR. The isolated cells exhibited a fibroblast-like morphology; expressed mesenchymal specific markers such as cluster of differentiation 73 (CD73), SRY (sex determining region Y)-box 2 (SOX-2), guanine nucleotide-binding protein-like 3 (GNL3), and stem cell factor receptor (SCFR); and could be differentiated into osteocytes and adipocytes that were characterized by Alizarin Red and Oil Red O staining. Under appropriate induction conditions, these cells were also able to differentiate into neuroglial-like or myocardial-like cells that expressed specific myocardial markers such as GATA transcription factors 4 (GATA-4), cardiac troponin T (cTnT), and myosin heavy chain 7B (MYH7B), or neural specific markers such as Nestin and glial fibrillary acidic protein (GFAP). This study demonstrated stem cells recovery and growth from giant pandas. The findings suggest that cells isolated from the BM of giant pandas have a high proliferative capacity and multiple differentiation potential in vitro which might aid conservation efforts.

  12. Heterogeneous vesicles in mucous epithelial cells of posterior esophagus of Chinese giant salamander (Andrias davidianus).

    PubMed

    Zhang, H; Guo, X; Zhong, S; Ge, T; Peng, S; Yu, P; Zhou, Z

    2015-08-25

    The Chinese giant salamander belongs to an old lineage of salamanders and endangered species. Many studies of breeding and disease regarding this amphibian had been implemented. However, the studies on the ultrastructure of this amphibian are rare. In this work, we provide a histological and ultrastructural investigation on posterior esophagus of Chinese giant salamander. The sections of amphibian esophagus were stained by hematoxylin & eosin (H&E). Moreover, the esophageal epithelium was observed by transmission electron microscopy (TEM). The results showed that esophageal epithelium was a single layer epithelium, which consisted of mucous cells and columnar cells. The esophageal glands were present in submucosa. The columnar cells were ciliated. According to the diverging ultrastructure of mucous vesicles, three types of mucous cells could be identified in the esophageal mucosa: i) electron-lucent vesicles mucous cell (ELV-MC); ii) electron-dense vesicles mucous cell (EDV-MC); and iii) mixed vesicles mucous cell (MV-MC).

  13. Incomplete cytokinesis and re-fusion of small mononucleated Hodgkin cells lead to giant multinucleated Reed-Sternberg cells.

    PubMed

    Rengstl, Benjamin; Newrzela, Sebastian; Heinrich, Tim; Weiser, Christian; Thalheimer, Frederic B; Schmid, Frederike; Warner, Kathrin; Hartmann, Sylvia; Schroeder, Timm; Küppers, Ralf; Rieger, Michael A; Hansmann, Martin-Leo

    2013-12-17

    Multinucleated Reed-Sternberg (RS) cells are pathognomonic for classical Hodgkin lymphoma (HL), and their presence is essential for diagnosis. How these giant tumor cells develop is controversial, however. It has been postulated that RS cells arise from mononucleated Hodgkin cells via endomitosis. Conversely, continuous single-cell tracking of HL cell lines by long-term time-lapse microscopy has identified cell fusion as the main route of RS cell formation. In contrast to growth-induced formation of giant Hodgkin cells, fusion of small mononuclear cells followed by a size increase gives rise to giant RS cells. Of note, fusion of cells originating from the same ancestor, termed re-fusion, is seen nearly exclusively. In the majority of cases, re-fusion of daughter cells is preceded by incomplete cytokinesis, as demonstrated by microtubule bonds among the cells. We confirm at the level of individual tracked cells that giant Hodgkin and RS cells have little proliferative capacity, further supporting small mononuclear Hodgkin cells as the proliferative compartment of the HL tumor clone. In addition, sister cells show a shared propensity for re-fusion, providing evidence of early RS cell fate commitment. Thus, RS cell generation is related neither to cell fusion of unrelated Hodgkin cells nor to endomitosis, but rather is mediated by re-fusion of daughter cells that underwent mitosis. This surprising finding supports the existence of a unique mechanism for the generation of multinuclear RS cells that may have implications beyond HL, given that RS-like cells are frequently observed in several other lymphoproliferative diseases as well.

  14. Incomplete cytokinesis and re-fusion of small mononucleated Hodgkin cells lead to giant multinucleated Reed–Sternberg cells

    PubMed Central

    Rengstl, Benjamin; Newrzela, Sebastian; Heinrich, Tim; Weiser, Christian; Thalheimer, Frederic B.; Schmid, Frederike; Warner, Kathrin; Hartmann, Sylvia; Schroeder, Timm; Küppers, Ralf; Rieger, Michael A.; Hansmann, Martin-Leo

    2013-01-01

    Multinucleated Reed–Sternberg (RS) cells are pathognomonic for classical Hodgkin lymphoma (HL), and their presence is essential for diagnosis. How these giant tumor cells develop is controversial, however. It has been postulated that RS cells arise from mononucleated Hodgkin cells via endomitosis. Conversely, continuous single-cell tracking of HL cell lines by long-term time-lapse microscopy has identified cell fusion as the main route of RS cell formation. In contrast to growth-induced formation of giant Hodgkin cells, fusion of small mononuclear cells followed by a size increase gives rise to giant RS cells. Of note, fusion of cells originating from the same ancestor, termed re-fusion, is seen nearly exclusively. In the majority of cases, re-fusion of daughter cells is preceded by incomplete cytokinesis, as demonstrated by microtubule bonds among the cells. We confirm at the level of individual tracked cells that giant Hodgkin and RS cells have little proliferative capacity, further supporting small mononuclear Hodgkin cells as the proliferative compartment of the HL tumor clone. In addition, sister cells show a shared propensity for re-fusion, providing evidence of early RS cell fate commitment. Thus, RS cell generation is related neither to cell fusion of unrelated Hodgkin cells nor to endomitosis, but rather is mediated by re-fusion of daughter cells that underwent mitosis. This surprising finding supports the existence of a unique mechanism for the generation of multinuclear RS cells that may have implications beyond HL, given that RS-like cells are frequently observed in several other lymphoproliferative diseases as well. PMID:24302766

  15. A Model of Giant Vacuole Dynamics in Human Schlemm’s Canal Endothelial Cells

    PubMed Central

    Pedrigi, Ryan M.; Simon, David; Reed, Ashley; Stamer, W. Daniel; Overby, Darryl R.

    2010-01-01

    Aqueous humour transport across the inner wall endothelium of Schlemm’s canal likely involves flow through giant vacuoles and pores, but the mechanics of how these structures form and how they influence the regulation of intraocular pressure (IOP) are not well understood. In this study, we developed an in vitro model of giant vacuole formation in human Schlemm’s canal endothelial cells (HSCECs) perfused in the basal-to-apical direction (i.e., the direction that flow crosses the inner wall in vivo) under controlled pressure drops (2 or 6 mmHg). The system was mounted on a confocal microscope for time-lapse en face imaging, and cells were stained with calcein, a fluorescent vital dye. At the onset of perfusion, elliptical void regions appeared within an otherwise uniformly stained cytoplasm, and 3-dimensional reconstructions revealed that these voids were dome-like outpouchings of the cell to form giant vacuole-like structures or GVLs that reproduced the classic “signet ring” appearance of true giant vacuoles. Increasing pressure drop from 2 to 6 mmHg increased GVL height (14 ± 4 vs. 21 ± 7 µm, p < 0.0001) and endothelial hydraulic conductivity (1.15 ± 0.04 vs. 2.11 ± 0.49 µL min−1 mmHg−1 cm−2; p < 0.001), but there was significant variability in the GVL response to pressure between cell lines isolated from different donors. During perfusion, GVLs were observed “migrating” and agglomerating about the cell layer and often collapsed despite maintaining the same pressure drop. GVL formation was also observed in human umbilical vein and porcine aortic endothelial cells, suggesting that giant vacuole formation is not a unique property of Schlemm’s canal cells. However, in these other cell types, GVLs were rarely observed “migrating” or contracting during perfusion, suggesting that Schlemm’s canal endothelial cells may be better adapted to withstand basal-to-apical directed pressure gradients. In conclusion, we have established an in vitro

  16. Recombinant production of biologically active giant grouper (Epinephelus lanceolatus) growth hormone from inclusion bodies of Escherichia coli by fed-batch culture.

    PubMed

    Chung, Wen-Jen; Huang, Chi-Lung; Gong, Hong-Yi; Ou, Tsung-Yin; Hsu, Jue-Liang; Hu, Shao-Yang

    2015-06-01

    Growth hormone (GH) performs important roles in regulating somatic growth, reproduction, osmoregulation, metabolism and immunity in teleosts, and thus, it has attracted substantial attention in the field of aquaculture application. Herein, giant grouper GH (ggGH) cDNA was cloned into the pET28a vector and expressed in Shuffle® T7 Competent Escherichia coli. Recombinant N-terminal 6× His-tagged ggGH was produced mainly in insoluble inclusion bodies; the recombinant ggGH content reached 20% of total protein. For large-scale ggGH production, high-cell density E. coli culture was achieved via fed-batch culture with pH-stat. After 30h of cultivation, a cell concentration of 41.1g/l dry cell weight with over 95% plasmid stability was reached. Maximal ggGH production (4.0g/l; 22% total protein) was achieved via mid-log phase induction. Various centrifugal forces, buffer pHs and urea concentrations were optimized for isolation and solubilization of ggGH from inclusion bodies. Hydrophobic interactions and ionic interactions were the major forces in ggGH inclusion body formation. Complete ggGH inclusion body solubilization was obtained in PBS buffer at pH 12 containing 3M urea. Through a simple purification process including Ni-NTA affinity chromatography and refolding, 5.7mg of ggGH was obtained from 10ml of fed-batch culture (45% recovery). The sequence and secondary structure of the purified ggGH were confirmed by LC-MS/MS mass spectrometry and circular dichroism analysis. The cell proliferation-promoting activity was confirmed in HepG2, ZFL and GF-1 cells with the WST-1 colorimetric bioassay. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Cytologic features of central giant-cell granuloma of the jaw.

    PubMed

    Gupta, Kirti; Dey, Pranab; Goldsmith, Ritalin; Vasishta, R K

    2004-08-01

    In this present series, we studied in detail the cytologic features of five histopathologically verified cases of central giant-cell granuloma (CGCG). All the patients in this series were female, with an age range of 11-60 years. There were three cases with involvement of the lower jaw and two cases had upper jaw involvement. Cytology smears showed dispersed single cells in the background. Nuclei of the individual cells were round to ovoid with fine chromatin and inconspicuous nucleoli. The cytoplasm of these cells was moderate in amount with indistinct cell borders. Many randomly scattered multinucleated giant cells with 10-20 nuclei were present in the background. Combination of clinical features, radiologic pictures, and cytologic features may be helpful for diagnosis of CGCG on fine-needle aspiration cytology. Copyright 2004 Wiley-Liss, Inc.

  18. Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells: a rare case report and review of the literature.

    PubMed

    Sah, Shambhu K; Li, Ying; Li, Yongmei

    2015-01-01

    Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCPOGC) is an extremely rare non-endocrine pancreatic tumor. To date, some cases have been reported, however, histogenesis and biologic behavior of UCPOGC remain controversial. We report a case of an UCPOGC in a 54-year-old female, who presented with a three-month history of recurrent abdominal pain without any incentive. Abdominal computed tomography (CT) revealed a large cystic mass of 10.5 × 9.3 cm in the body and tail of the pancreas compressing the adjacent bowel loop and stomach. The preliminary diagnosis was considered as a malignant tumor of body and tail of the pancreas. The patient had open distal pancreatic mass resection with splenectomy and according to the results of histopathological and immunohistochemical studies, the diagnosis of an UCPOGC was established.

  19. [Giant cell tumours in a pyramidal bone: a clinical case and a review of the literature].

    PubMed

    Gutiérrez-Santiago, M M; González-Arteaga, J; Hidalgo-Ovejero, A M

    2012-01-01

    Giant cell tumours (GCT) of the bone are benign, but locally invasive tumours. We present a new case of carpus GCT, involving the triquetrum. The diagnosis required a prior biopsy before doing the block resection. This treatment is the best option to avoid recurrences. We review the literature on this particular lesion in the carpus bone.

  20. Primary ciliary dyskinesia: Kartagener syndrome with central giant cell granuloma. A case report.

    PubMed

    Türkoğlu, Kivanç; Orhan, Kaan; Demir, Pinar; Karabulut, Bariş; Can-Karabulut, Deniz C

    2010-10-01

    This paper describes a clinical case of both giant cell granuloma and Kartagener syndrome in a 15-year-old male patient, with emphasis on the radiographic aspects of this extremely unusual pathology. To our knowledge, the presence of these 2 rare clinical conditions in the same patient has not been previously reported.

  1. Quantitative analysis of argyrophilic nuclear organizer regions in giant cell lesions of jaws.

    PubMed

    Sadri, Donia; Hejazi, Massoud; Jahanbani, Jahanfar; Forouzandeh, Aghdas

    2010-05-01

    Giant cell lesions of the jaws are considerably similar according to histopathologic characteristics yet show different clinical behaviors. These lesions include central giant cell granuloma (CGCG), aneurysmal bone cyst, Cherubism, and Brown tumor associated with hyperparathyroidism. The present study aimed to investigate AgNORs count in these lesions as a proliferative marker and to determine whether it can be used to discriminate between them or not. Forty-one cases of giant cell lesions of jaws were retrived from Oral Pathology Department (1987-2007). They included 21 cases of CGCG, eight cases of aneurysmal bone cyst (ABC), six cases of Cherubism, six cases of Brown tumor. The mean AgNORs count was calculated for all cases. To compare mean AgNORs in groups of lesions, ANOVA test was performed. Mean AgNOR counts were: (0/85 +/- 0/29) in CGCG, (0/76 +/- 0/32) in ABC (0/87 +/- 0/10) in Cherubism and (0/82 +/- 0/16) in Brown tumor. A significant difference was not observed in AgNOR counts among these groups of lesions. Jaws giant cell containing lesions have no acceptable differences in mean AgNORs.

  2. Suspected Giant cell aortitis : from multiple aortic structural damage to fatal listeria sepsi. A case report.

    PubMed

    Silvestri, Valeria; Isernia, Giacomo

    2017-03-16

    Giant cell arteritis ( GCA) is an inflammatory vasculopathy affecting large and middle-sized vessels , specifically cranial arteries derived from carotid artery. Isolated extracranial vessel involvement can occur. Interest in extravascular manifestations is recently increasing because of diffusion of sensitive and specific imaging tools such as 18FDG PET TC . Patients have an increased relative risk of severe infection. Listeria monocytogenes infection risk is increased, and vascular system involvement and graft infection have been, even though rarely, reported. We report the case of a 72 year old woman with a history of suspected giant cell aortitis , previous surgical treatment of ascendant and descendant thoracic aortic aneurysm, presenting 7 year after TEVAR with thoracic pain , fever, inflammatory indexes increase, leukocytosis, listeria sepsis and rapidly increasing type I proximal endoleak on CT. 18 FDG PET positivity was associated. Endograft listeria infection on aortitis reactivation was suspected but death for multi-organ failure and absence of autopsy data couldn't confirm diagnosis . Listeria vascular graft infection has been reported previously. Giant cell arteritis is a predisposing condition. We report the first case of endograft infection by listeria monocytogenes in a patient with positive history of suspected giant cell aortic aneurysm.

  3. Generation of cancer stem-like cells through the formation of polyploid giant cancer cells.

    PubMed

    Zhang, S; Mercado-Uribe, I; Xing, Z; Sun, B; Kuang, J; Liu, J

    2014-01-02

    Polyploid giant cancer cells (PGCCs) have been observed by pathologists for over a century. PGCCs contribute to solid tumor heterogeneity, but their functions are largely undefined. Little attention has been given to these cells, largely because PGCCs have been generally thought to originate from repeated failure of mitosis/cytokinesis and have no capacity for long-term survival or proliferation. Here we report our successful purification and culture of PGCCs from human ovarian cancer cell lines and primary ovarian cancer. These cells are highly resistant to oxygen deprivation and could form through endoreduplication or cell fusion, generating regular-sized cancer cells quickly through budding or bursting similar to simple organisms like fungi. They express normal and cancer stem cell markers, they divide asymmetrically and they cycle slowly. They can differentiate into adipose, cartilage and bone. A single PGCC formed cancer spheroids in vitro and generated tumors in immunodeficient mice. These PGCC-derived tumors gained a mesenchymal phenotype with increased expression of cancer stem cell markers CD44 and CD133 and become more resistant to treatment with cisplatin. Taken together, our results reveal that PGCCs represent a resistant form of human cancer using an ancient, evolutionarily conserved mechanism in response to hypoxia stress; they can contribute to the generation of cancer stem-like cells, and also play a fundamental role in regulating tumor heterogeneity, tumor growth and chemoresistance in human cancer.

  4. Differential expression of filamin B splice variants in giant cell tumor cells

    PubMed Central

    Tsui, Joseph Chi-Ching; Lau, Carol Po-Ying; Cheung, Alex Chun; Wong, Kwok-Chuen; Huang, Lin; Tsui, Stephen Kwok-Wing; Kumta, Shekhar Madhukar

    2016-01-01

    Giant cell tumor of bone (GCT) is the most commonly reported non-malignant bone tumor in Hong Kong. This kind of tumor usually affects people aged 20–40 years. Also, it is well known for recurrence locally, especially when the tumor cannot be removed completely. Filamins are actin-binding proteins which contain three family members, filamin A, B and C. They are the products of three different genes, FLNA, FLNB and FLNC, which can generate various transcript variants in different cell types. In this study, we focused on the effects of FLNBv2 and FLNBv4 toward GCT cells. The only difference between FLNBv2 and FLNBv4 is that FLNBv4 does not contain hinge 1 region. We found that the relative abundance of FLNBv4 varies among different GCT cell lines while the expression level of FLNBv4 in normal osteoblasts was only marginally detectable. In the functional aspect, overexpression of FLNBv4 led to upregulation of RANKL, OCN, OPG and RUNX2, which are closely related to GCT cell survival and differentiation. Moreover, FLNBv4 can have a negative effect on cell viability of GCT cells when compare with FLNBv2. In conclusion, splicing variants of FLNB are differentially expressed in GCT cells and may play a role in the proliferation and differentiation of tumor cells. PMID:27779699

  5. Structure-Guided Blockade of CSF1R Kinase in Tenosynovial Giant-Cell Tumor.

    PubMed

    Tap, William D; Wainberg, Zev A; Anthony, Stephen P; Ibrahim, Prabha N; Zhang, Chao; Healey, John H; Chmielowski, Bartosz; Staddon, Arthur P; Cohn, Allen Lee; Shapiro, Geoffrey I; Keedy, Vicki L; Singh, Arun S; Puzanov, Igor; Kwak, Eunice L; Wagner, Andrew J; Von Hoff, Daniel D; Weiss, Glen J; Ramanathan, Ramesh K; Zhang, Jiazhong; Habets, Gaston; Zhang, Ying; Burton, Elizabeth A; Visor, Gary; Sanftner, Laura; Severson, Paul; Nguyen, Hoa; Kim, Marie J; Marimuthu, Adhirai; Tsang, Garson; Shellooe, Rafe; Gee, Carolyn; West, Brian L; Hirth, Peter; Nolop, Keith; van de Rijn, Matt; Hsu, Henry H; Peterfy, Charles; Lin, Paul S; Tong-Starksen, Sandra; Bollag, Gideon

    2015-07-30

    Expression of the colony-stimulating factor 1 (CSF1) gene is elevated in most tenosynovial giant-cell tumors. This observation has led to the discovery and clinical development of therapy targeting the CSF1 receptor (CSF1R). Using x-ray co-crystallography to guide our drug-discovery research, we generated a potent, selective CSF1R inhibitor, PLX3397, that traps the kinase in the autoinhibited conformation. We then conducted a multicenter, phase 1 trial in two parts to analyze this compound. In the first part, we evaluated escalations in the dose of PLX3397 that was administered orally in patients with solid tumors (dose-escalation study). In the second part, we evaluated PLX3397 at the chosen phase 2 dose in an extension cohort of patients with tenosynovial giant-cell tumors (extension study). Pharmacokinetic and tumor responses in the enrolled patients were assessed, and CSF1 in situ hybridization was performed to confirm the mechanism of action of PLX3397 and that the pattern of CSF1 expression was consistent with the pathological features of tenosynovial giant-cell tumor. A total of 41 patients were enrolled in the dose-escalation study, and an additional 23 patients were enrolled in the extension study. The chosen phase 2 dose of PLX3397 was 1000 mg per day. In the extension study, 12 patients with tenosynovial giant-cell tumors had a partial response and 7 patients had stable disease. Responses usually occurred within the first 4 months of treatment, and the median duration of response exceeded 8 months. The most common adverse events included fatigue, change in hair color, nausea, dysgeusia, and periorbital edema; adverse events rarely led to discontinuation of treatment. Treatment of tenosynovial giant-cell tumors with PLX3397 resulted in a prolonged regression in tumor volume in most patients. (Funded by Plexxikon; ClinicalTrials.gov number, NCT01004861.).

  6. A mouse model of luciferase-transfected stromal cells of giant cell tumor of bone.

    PubMed

    Lau, Carol P Y; Wong, Kwok Chuen; Huang, Lin; Li, Gang; Tsui, Stephen K W; Kumta, Shekhar Madhukar

    2015-11-01

    A major barrier towards the study of the effects of drugs on Giant Cell Tumor of Bone (GCT) has been the lack of an animal model. In this study, we created an animal model in which GCT stromal cells survived and functioned as proliferating neoplastic cells. A proliferative cell line of GCT stromal cells was used to create a stable and luciferase-transduced cell line, Luc-G33. The cell line was characterized and was found that there were no significant differences on cell proliferation rate and recruitment of monocytes when compared with the wild type GCT stromal cells. We delivered the Luc-G33 cells either subcutaneously on the back or to the tibiae of the nude mice. The presence of viable Luc-G33 cells was assessed using real-time live imaging by the IVIS 200 bioluminescent imaging (BLI) system. The tumor cells initially propagated and remained viable on site for 7 weeks in the subcutaneous tumor model. We also tested in vivo antitumor effects of Zoledronate (ZOL) and Geranylgeranyl transferase-I inhibitor (GGTI-298) alone or their combinations in Luc-G33-transplanted nude mice. ZOL alone at 400 µg/kg and the co-treatment of ZOL at 400 µg/kg and GGTI-298 at 1.16 mg/kg reduced tumor cell viability in the model. Furthermore, the anti-tumor effects by ZOL, GGTI-298 and the co-treatment in subcutaneous tumor model were also confirmed by immunohistochemical (IHC) staining. In conclusion, we established a nude mice model of GCT stromal cells which allows non-invasive, real-time assessments of tumor development and testing the in vivo effects of different adjuvants for treating GCT.

  7. Involvement and prognosis value of CD8(+) T cells in giant cell arteritis.

    PubMed

    Samson, Maxime; Ly, Kim Heang; Tournier, Benjamin; Janikashvili, Nona; Trad, Malika; Ciudad, Marion; Gautheron, Alexandrine; Devilliers, Hervé; Quipourt, Valérie; Maurier, François; Meaux-Ruault, Nadine; Magy-Bertrand, Nadine; Manckoundia, Patrick; Ornetti, Paul; Maillefert, Jean-Francis; Besancenot, Jean-François; Ferrand, Christophe; Mesturoux, Laura; Labrousse, François; Fauchais, Anne-Laure; Saas, Philippe; Martin, Laurent; Audia, Sylvain; Bonnotte, Bernard

    2016-08-01

    CD8(+) T cells participate in the pathogenesis of some vasculitides. However, little is known about their role in Giant Cell Arteritis (GCA). This study was conducted to investigate CD8(+) T cell involvement in the pathogenesis of GCA. Analyses were performed at diagnosis and after 3 months of glucocorticoid treatment in 34 GCA patients and 26 age-matched healthy volunteers. Percentages of CD8(+) T-cell subsets, spectratype analysis of the TCR Vβ families of CD8(+) T cells, levels of cytokines and chemokines and immunohistochemistry of temporal artery biopsies (TAB) were assessed. Among total CD8(+) T cells, percentages of circulating cytotoxic CD8 T lymphocytes (CTL, CD3(+)CD8(+)perforin(+)granzymeB(+)), Tc17 (CD3(+)CD8(+)IL-17(+)), CD63(+)CD8(+) T cells and levels of soluble granzymes A and B were higher in patients than in controls, whereas the percentage of Tc1 cells (CD3(+)CD8(+)IFN-γ(+)) was similar. Moreover, CD8(+) T cells displayed a restricted TCR repertoire in GCA patients. Percentages of circulating CTL, Tc17 and soluble levels of granzymes A and B decreased after treatment. CXCR3 expression on CD8(+) T cells and its serum ligands (CXCL9, -10, -11) were higher in patients. Analyses of TAB revealed high expression of CXCL9 and -10 associated with infiltration by CXCR3(+)CD8(+) T cells expressing granzyme B and TiA1. The intensity of the CD8 T-cell infiltrate in TAB was predictive of the severity of the disease. This study demonstrates the implication and the prognostic value of CD8(+) T-cells in GCA and suggests that CD8(+) T-cells are recruited within the vascular wall through an interaction between CXCR3 and its ligands. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Radioiodine Accumulation in a Giant Ovarian Cystadenofibroma Detected Incidentally by 131-I Whole Body Scans

    PubMed Central

    Mebarki, Mohammed; Menemani, Abdelghani; Medjahedi, Abdelkader; Boualou, Fouad; Slama, Abdelhak; Ouguirti, Sarah; Kherbouche, Fatima Zahra; Berber, Nécib

    2012-01-01

    Ovarian cystadenofibroma is a relatively rare tumor; it is usually asymptomatic and is found incidentally. We present the case of a 24-year-old female patient, who had undergone total thyroidectomy for thyroid papillary carcinoma, with an asymptomatic giant cystadenofibroma, incidentally discovered by diagnostic 131I-SPECT/CT WBSs. We summarize the clinical history, imaging data, and histopathological study on a rare case of radioiodine accumulation in cystadenofibroma, and we discuss the mechanism of uptake of radioiodine in this case. PMID:23119215

  9. The activation pattern of macrophages in giant cell (temporal) arteritis and primary angiitis of the central nervous system.

    PubMed

    Mihm, Bernhard; Bergmann, Markus; Brück, Wolfgang; Probst-Cousin, Stefan

    2014-06-01

    To determine if the pattern of macrophage activation reflects differences in the pathogenesis and clinical presentation of giant cell arteritis and primary angiitis of the central nervous system, specimens of 10 patients with giant cell arteritis and five with primary angiitis of the central nervous system were immunohistochemically studied and the expression of the macrophage activation markers 27E10, MRP14, MRP8 and 25F9 was determined in the vasculitic infiltrates. Thus, a partly different expression pattern of macrophage activation markers in giant cell arteritis and primary angiitis of the central nervous system was observed. The group comparison revealed that giant cell arteritis cases had significantly higher numbers of acute activated MRP14-positive macrophages, whereas primary angiitis of the central nervous system is characterized by a tendency toward more MRP8-positive intermediate/late activated macrophages. Furthermore, in giant cell arteritis comparably fewer CD8-positive lymphocytes were observed. These observations suggest, that despite their histopathological similarities, giant cell arteritis and primary angiitis of the central nervous system appear to represent either distinct entities within the spectrum of granulomatous vasculitides or different stages of similar disease processes. Their discrete clinical presentation is reflected by different activation patterns of macrophages, which may characterize giant cell arteritis as a more acute process and primary angiitis of the central nervous system as a more advanced inflammatory process. © 2013 Japanese Society of Neuropathology.

  10. Characteristics of cerebrovascular accidents at time of diagnosis in a series of 98 patients with giant cell arteritis.

    PubMed

    Zenone, Thierry; Puget, Marie

    2013-12-01

    The objective of this study was to determine the characteristics of cerebrovascular accidents at time of diagnosis in patients with giant cell arteritis. Retrospective data were collected from 98 patients at a single hospital with giant cell arteritis (according to the American College of Rheumatology classification criteria) diagnosed between October 1999 and January 2012. Cerebrovascular accident was found at initial presentation in 6 patients (6.1 %, 95 % CIs 2.3-12.9). Most of them had other symptoms of giant cell arteritis when the disease began. Signs reflecting the involvement of vertebro-basilar territory were present in 3 cases. No other case of cerebrovascular accident was described during the follow-up of patient; particularly no case of cerebrovascular accident occurred once corticosteroid therapy for the treatment of giant cell arteritis had been initiated. No differences in the epidemiologic, clinical and laboratory features at the time of diagnosis between patients who had cerebrovascular accidents and the rest of the giant cell arteritis patients were observed. Prognosis was good in our survey. However, there was no case of bilateral vertebral artery occlusion, a condition associated with poor prognosis. The present study confirms that cerebrovascular accidents may be the initial manifestation of giant cell arteritis, an argument in favor of a direct effect of the vasculitis in the development of cerebrovascular accidents rather than a complication of the corticosteroid therapy. The diagnosis of giant cell arteritis should always be considered in an elderly patient with stroke and an unexplained elevation of inflammatory biomarkers.

  11. Correlation of Histopathologic Features with Demographic, Gross and Radiographic Findings in Giant Cell Granulomas of the Jaws

    PubMed Central

    Aghbali, Amirala; Sina, Mahmood; Vahid Pakdel, Seyyed Mahdi; Emamverdizadeh, Parya; Kouhsoltani, Maryam; Mahmoudi, Seyyed Mostafa; Janani, Maryam

    2013-01-01

    Background and aims. The correlation between morphology of giant cells in peripheral granulomas of the jaws and the aggressive behavior of the lesion is unknown. This study investigated the correlation between the histopathologic features with demographic, gross and radiographic findings in giant cell granulomas. Materials and methods. In this analytical study, data from 23 cases of central giant cell granuloma (CGCG) and 42 cases of peripheral giant cell granuloma (PGCG) were analyzed, focusing on age, gender, location, and gross and radiographic features. For each patient, microscopic slides were assessed in terms of histologic features of giant cells and stroma. Results. No significant differences were found in the mean number of nuclei or the size of nuclei and giant cell distribution patterns between the jaws and genders in both lesions (P >0.05). Correlation between the mean number of nuclei and age was positively significant and correlation between the size of nuclei and age was negatively significant (P < 0.05). In addition, correlation between the mean number and size of nuclei and the size of the lesion was significant (P < 0.05). Correlation between stroma and aggressiveness of CGCGs was not statistically significant. Correlation between histopathologic features and radiographic findings was not statistically significant (P > 0.05). Conclusion. There were correlations between the mean number of nuclei per giant cell and the size of the lesion and age, and between the size of nuclei and size of the lesion. No relation was observed between histopathologic and radiographic features. PMID:24578821

  12. Doublecortin immunoreactivity in giant cells of tuberous sclerosis and focal cortical dysplasia.

    PubMed

    Mizuguchi, Masashi; Yamanouchi, Hideo; Becker, Laurence E; Itoh, Masayuki; Takashima, Sachio

    2002-10-01

    Cerebral cortical lesions of tuberous sclerosis (TSC) and focal cortical dysplasia (FCD) show disturbances in laminar architecture and cellular differentiation. We immunohistochemically studied the expression of doublecortin, a fetal neuronal protein that regulates neuronal migration, in the surgical specimens of five TSC and eight FCD patients. In both TSC and FCD, bizarre giant cells showed a variable degree of doublecortin immunoreactivity. Both cytomegalic neurons and balloon cells were positive. The staining tended to be more intense in TSC than in FCD, although there were exceptional cases in both groups. Doublecortin immunoreactivity of normal-sized neural cells was restricted to a small number of astrocytes, and comparable to that in control patients. The persistent expression of doublecortin by giant cells in the postnatal cerebrum is additional evidence of abnormal differentiation, which may be relevant to the pathogenesis of cortical disarray in TSC and FCD.

  13. Intraoperative squash cytology and histology of giant cell ependymoma: A diagnostic dilemma

    PubMed Central

    Cakir, Ebru; Kucuk, Ulku; Ersen, Ayca; Pala, Emel E; Senoglu, Mehmet; Binatli, Ali O; Yildirim, Zubeyde

    2017-01-01

    Giant cell ependymomas (GCE) are extremely rare tumors, with 24 cases described in the literature. Squash cytology is a rapid, reliable, simple technique for intraoperative consultation in neurosurgical practice. We describe a rare case of GCE arising at level of L4-L5 in a 66-year-old woman and discuss the cytologic/histologic features. Intraoperative smears were highly cellular with a prominent fibrillary background and exhibited papillary structures and sheets composed of highly atypical and bizarre cells. Some of the cells showed nuclear pseudoinclusions and rarely formed pseudorosette-like arrays. Intraoperative diagnosis was high grade glial tumor. On paraffin sections, besides extensive polymorphism, there were no microvascular proliferation, necrosis, and mitosis and the final diagnosis was WHO grade II GCE. GCE may be a diagnostic challenge on intraoperative smears, frozen, and paraffin sections. It must be kept in mind in the differential diagnosis of giant cell exhibiting benign and malignant tumors of brain. PMID:28182061

  14. Giant cell-rich osteosarcoma of the parotid gland: An exceptionally rare entity at an unusual site.

    PubMed

    Huang, Eric C; Ghazikhanian, Varand; Qian, Xiaohua

    2016-12-01

    Giant cell-rich osteosarcoma is a rare histologic variant of conventional osteosarcoma that affects mainly the extremities. Extraskeletal giant cell-rich osteosarcoma is therefore exceedingly rare. Here, we report the first case of this uncommon tumor involving the parotid gland in a 62-year-old male who presented with initial right jaw swelling. Radiologic work-up revealed a 6.2 cm mass involving the right parotid gland. Fine-needle aspiration cytology showed numerous multinucleated giant cells in a background of dyshesive epithelioid cells and rare clusters of spindle stromal cells, suspicious for malignancy. The subsequent excisional biopsy showed histopathologic features diagnostic for giant cell-rich osteosarcoma. Diagn. Cytopathol. 2016;44:1107-1111. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Everolimus in the treatment of subependymal giant cell astrocytomas, angiomyolipomas, and pulmonary and skin lesions associated with tuberous sclerosis complex

    PubMed Central

    Franz, David Neal

    2013-01-01

    Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder caused by inactivating mutations in either the TSC1 or TSC2 genes. It is characterized by the development of multiple, benign tumors in several organs throughout the body. Lesions occur in the brain, kidneys, heart, liver, lungs, and skin and result in seizures and epilepsy, mental retardation, autism, and renal and pulmonary organ system dysfunction, as well as other complications. Elucidation of the molecular pathways and etiological factors responsible for causing TSC has led to a paradigm shift in the management and treatment of the disease. TSC1 or TSC2 mutations lead to constitutive upregulation of the mammalian target of rapamycin pathway, which affects many cellular processes involved in tumor growth. By targeting mammalian target of rapamycin with everolimus, an orally active rapamycin derivative, clinically meaningful and statistically significant reductions in tumor burden have been achieved for the main brain (subependymal giant cell astrocytoma) and renal manifestations (angiomyolipoma) associated with TSC. This review provides an overview of TSC, everolimus, and the clinical trials that led to its approval for the treatment of TSC-associated subependymal giant cell astrocytoma and renal angiomyolipoma. PMID:24143074

  16. Giant Panda (Ailuropoda melanoleuca) Buccal Mucosa Tissue as a Source of Multipotent Progenitor Cells.

    PubMed

    Prescott, Hilary M A; Manning, Craig; Gardner, Aaron; Ritchie, William A; Pizzi, Romain; Girling, Simon; Valentine, Iain; Wang, Chengdong; Jahoda, Colin A B

    2015-01-01

    Since the first mammal was cloned, the idea of using this technique to help endangered species has aroused considerable interest. However, several issues limit this possibility, including the relatively low success rate at every stage of the cloning process, and the dearth of usable tissues from these rare animals. iPS cells have been produced from cells from a number of rare mammalian species and this is the method of choice for strategies to improve cloning efficiency and create new gametes by directed differentiation. Nevertheless information about other stem cell/progenitor capabilities of cells from endangered species could prove important for future conservation approaches and adds to the knowledge base about cellular material that can be extremely limited. Multipotent progenitor cells, termed skin-derived precursor (SKP) cells, can be isolated directly from mammalian skin dermis, and human cheek tissue has also been shown to be a good source of SKP-like cells. Recently we showed that structures identical to SKPs termed m-SKPs could be obtained from monolayer/ two dimensional (2D) skin fibroblast cultures. Here we aimed to isolate m-SKPs from cultured cells of three endangered species; giant panda (Ailuropoda melanoleuca); red panda (Ailurus fulgens); and Asiatic lion (Panthera leo persica). m-SKP-like spheres were formed from the giant panda buccal mucosa fibroblasts; whereas dermal fibroblast (DF) cells cultured from abdominal skin of the other two species were unable to generate spheres. Under specific differentiation culture conditions giant panda spheres expressed neural, Schwann, adipogenic and osteogenic cell markers. Furthermore, these buccal mucosa derived spheres were shown to maintain expression of SKP markers: nestin, versican, fibronectin, and P75 and switch on expression of the stem cell marker ABCG2. These results demonstrate that giant panda cheek skin can be a useful source of m-SKP multipotent progenitors. At present lack of sample numbers

  17. Giant Panda (Ailuropoda melanoleuca) Buccal Mucosa Tissue as a Source of Multipotent Progenitor Cells

    PubMed Central

    Prescott, Hilary M. A.; Manning, Craig; Gardner, Aaron; Ritchie, William A.; Pizzi, Romain; Girling, Simon; Valentine, Iain; Wang, Chengdong; Jahoda, Colin A. B.

    2015-01-01

    Since the first mammal was cloned, the idea of using this technique to help endangered species has aroused considerable interest. However, several issues limit this possibility, including the relatively low success rate at every stage of the cloning process, and the dearth of usable tissues from these rare animals. iPS cells have been produced from cells from a number of rare mammalian species and this is the method of choice for strategies to improve cloning efficiency and create new gametes by directed differentiation. Nevertheless information about other stem cell/progenitor capabilities of cells from endangered species could prove important for future conservation approaches and adds to the knowledge base about cellular material that can be extremely limited. Multipotent progenitor cells, termed skin-derived precursor (SKP) cells, can be isolated directly from mammalian skin dermis, and human cheek tissue has also been shown to be a good source of SKP-like cells. Recently we showed that structures identical to SKPs termed m-SKPs could be obtained from monolayer/ two dimensional (2D) skin fibroblast cultures. Here we aimed to isolate m-SKPs from cultured cells of three endangered species; giant panda (Ailuropoda melanoleuca); red panda (Ailurus fulgens); and Asiatic lion (Panthera leo persica). m-SKP-like spheres were formed from the giant panda buccal mucosa fibroblasts; whereas dermal fibroblast (DF) cells cultured from abdominal skin of the other two species were unable to generate spheres. Under specific differentiation culture conditions giant panda spheres expressed neural, Schwann, adipogenic and osteogenic cell markers. Furthermore, these buccal mucosa derived spheres were shown to maintain expression of SKP markers: nestin, versican, fibronectin, and P75 and switch on expression of the stem cell marker ABCG2. These results demonstrate that giant panda cheek skin can be a useful source of m-SKP multipotent progenitors. At present lack of sample numbers

  18. Denosumab-Treated Giant Cell Tumor of Bone Its Histologic Spectrum and Potential Diagnostic Pitfalls.

    PubMed

    Roitman, Pablo Daniel; Jauk, Federico; Farfalli, Germán Luis; Albergo, José Ignacio; Aponte-Tinao, Luis Alberto

    2017-02-21

    Giant cell tumor of bone (GCT) is a locally aggressive, rarely metastasizing primary bone neoplasm that occurs most frequently in the epiphysis of long bones of young adults. It is composed of round, oval or elongated mononuclear cells admixed with osteoclast-like giant cells that express receptor activator of nuclear factor- қB (RANK). The mononuclear stromal cells express RANK ligand (RANKL), a mediator of osteoclast activation. Denosumab, a monoclonal antibody that inhibits RANKL reducing tumor-associated bone lysis, has been used to treat selected cases of GCT. We reviewed the clinical records and histologic slides of 9 patients with GCT that had received denosumab therapy and were subsequently surgically treated. There were 5 males and 4 females, aged 20 to 66 (mean 36). Duration of treatment varied from 2,5 to 13months (mean 5,9). In all cases, different degrees of ossification, fibrosis, depletion of giant cells and proliferation of mononuclear cells were seen. With this combination of changes, denosumab-treated GCT may mimick other lesions such as fibrous dysplasia, juvenile ossifying fibroma, nonossifying fibroma and osteoblastoma. Less frequent but more relevant is the presence of cellular atypia or patterns of ossification that resemble an undifferentiated pleomorphic sarcoma, a conventional osteosarcoma or a low-grade central osteosarcoma. The presence of clinical and radiological response to denosumab along with the lack of high mitotic activity, atypical mitotic figures, extensive necrosis or a permeative pattern of growth, represent clues to achieve a correct diagnosis.

  19. Denosumab, a Potential Alternative to the Surgical Treatment of Distal Radius Giant Cell Tumor of Bone: Case Report.

    PubMed

    Park, Min Jung; Ganjoo, Kristen N; Ladd, Amy L

    2015-08-01

    Juxta-articular giant cell tumors can pose major surgical challenges. Aggressive distal radius giant cell tumors often require complex reconstructive procedures that are associated with numerous complications. We present a case of a 25-year old man with a Campanacci grade 3 giant cell tumor of the distal radius that was successfully treated with denosumab without complex reconstructive procedures. At 3.5-year follow-up and 1-year drug free period, the patient remained asymptomatic without histologic evidence of recurrent tumor. With denosumab therapy, patients can potentially avoid surgery and achieve a successful outcome.

  20. Jejunal intussusception caused by metastasis of a giant cell carcinoma of the lung

    PubMed Central

    Fujii, Yuki; Homma, Shigenori; Yoshida, Tadashi; Taketomi, Akinobu

    2016-01-01

    A 55-year-old woman was admitted to our hospital reporting of nausea, vomiting and anorexia. One month before admission, she had been diagnosed with lung cancer with intestinal metastasis. A CT scan confirmed intussusception due to intestinal metastasis and she underwent emergency laparoscopic surgery followed by resection of the primary lung cancer. Histopathological findings of the intestinal specimen suggested the metastasis was from a giant cell carcinoma of the lung, which had extensive necrosis. She was still alive without recurrence 11 months after the first surgery. Giant cell carcinoma of the lung is a rare type of non-small cell carcinoma and intestinal metastasis is one of the unique features. This type of tumour has such aggressive characteristics that oncological prognosis is reported to be extremely poor. In our case, however, complete surgical resection of both primary and metastatic tumours might result in a better outcome than has been reported. PMID:27485876

  1. Synchronous Multicentric Giant Cell Tumour (GCT)-A Rare Case Report.

    PubMed

    Shekhar, Anshu; Murgod, Gururaj; Korlhalli, Suresh

    2014-02-01

    Giant Cell Tumours (GCT) of bone account for 5% of all primary bone tumours. Multicentric variety is a rare variant of this condition, accounting for less than 1% of all cases and can occur as synchronous or metachronous lesions. We report a 22-year-old male patient with 18 months history of painful progressive swellings around the right knee. Radiographs revealed expansile lytic lesions in the distal femur, proximal tibia and fibula and core needle biopsy was typical of GCT. Biochemical parameters were normal and radiological investigations did not reveal any metastasis. The patient was treated by above knee amputation due to the extensive nature of the tumours. The excised tissue from all sites had features of giant cell tumor with no atypia or malignant cells seen. The patient is free from recurrence or metastasis at three years follow up.

  2. Effect of Instant Cooked Giant Embryonic Rice on Body Fat Weight and Plasma Lipid Profile in High Fat-Fed Mice

    PubMed Central

    Chung, Soo Im; Kim, Tae Hyeong; Rico, Catherine W.; Kang, Mi Young

    2014-01-01

    The comparative effects of instant cooked rice made from giant embryo mutant or ordinary normal rice on body weight and lipid profile in high fat-fed mice were investigated. The animals were given experimental diets for seven weeks: normal control (NC), high fat (HF), and HF supplemented with instant normal white (HF-NW), normal brown (HF-NB), giant embryonic white (HF-GW), or giant embryonic brown (HF-GB) rice. The HF group showed markedly higher body weight, body fat, plasma and hepatic triglyceride and cholesterol concentrations, and atherogenic index relative to NC group. However, instant rice supplementation counteracted this high fat-induced hyperlipidemia through regulation of lipogenesis and adipokine production. The GB rice exhibited greater hypolipidemic and body fat-lowering effects than the GW or NB rice. These findings illustrate that the giant embryo mutant may be useful as functional biomaterial for the development of instant rice with strong preventive action against high fat diet-induced hyperlipidemia and obesity. PMID:24932656

  3. Effect of instant cooked giant embryonic rice on body fat weight and plasma lipid profile in high fat-fed mice.

    PubMed

    Chung, Soo Im; Kim, Tae Hyeong; Rico, Catherine W; Kang, Mi Young

    2014-06-13

    The comparative effects of instant cooked rice made from giant embryo mutant or ordinary normal rice on body weight and lipid profile in high fat-fed mice were investigated. The animals were given experimental diets for seven weeks: normal control (NC), high fat (HF), and HF supplemented with instant normal white (HF-NW), normal brown (HF-NB), giant embryonic white (HF-GW), or giant embryonic brown (HF-GB) rice. The HF group showed markedly higher body weight, body fat, plasma and hepatic triglyceride and cholesterol concentrations, and atherogenic index relative to NC group. However, instant rice supplementation counteracted this high fat-induced hyperlipidemia through regulation of lipogenesis and adipokine production. The GB rice exhibited greater hypolipidemic and body fat-lowering effects than the GW or NB rice. These findings illustrate that the giant embryo mutant may be useful as functional biomaterial for the development of instant rice with strong preventive action against high fat diet-induced hyperlipidemia and obesity.

  4. Papanicolaou staining of exfoliated vaginal epithelial cells facilitates the prediction of ovulation in the giant panda.

    PubMed

    Durrant, B; Czekala, N; Olson, M; Anderson, A; Amodeo, D; Campos-Morales, R; Gual-Sill, F; Ramos-Garza, J

    2002-04-15

    The giant panda is seasonally monoestrus, experiencing a single estrous with spontaneous ovulation in the spring. Therefore, accurate monitoring of the estrous cycle to pinpoint the time of ovulation is critical for the success of timed mating or artificial insemination. Analysis of exfoliated vaginal epithelial cells is a simple technique that rapidly yields information about the estrous status of a panda. Vaginal swabs were obtained during five estrous cycles of two nulliparous females. Cells were stained with the trichrome Papanicolaou and classified as basophils, intermediates or superficials. The color of stained cells, basophilic, acidophilic or keratinized, was recorded as a characteristic independent of the three standard cell types. The day urinary conjugates of estrogen fell from peak levels was considered the day of ovulation. A chromic shift occurred 8-9 days before ovulation when the majority of exfoliated vaginal cells changed from basophilic (blue) to acidophilic (pink) without accompanying nuclear or cytoplasmic changes. A second chromic shift was consistently observed 2 days prior to ovulation when keratinized (orange) cells replaced acidophils as the majority of vaginal cells. Monochrome staining of vaginal cells is sufficient to quantify superficial cells, which is a useful adjunct to behavioral and endocrinological data in determining estrous in the giant panda. However, the timing and duration of superficial cell elevations are substantially different between and within individual females, which limits the accuracy of timing ovulation for artificial insemination. The predictive value of vaginal cytology was greatly enhanced with the trichrome stain and evaluation of cell color.

  5. Giant basal cell carcinoma of the face: surgical management and challenges for reconstruction.

    PubMed

    Maimaiti, A; Mijiti, A; Yarbag, A; Moming, A

    2016-02-01

    Giant basal cell carcinoma, in which the tumour measures 5 cm or greater in diameter, is a very rare skin malignancy that accounts for less than 1 per cent of all basal cell tumours. Very few studies have reported on the incidence, resection and reconstruction of this lesion worldwide. In total, 17 patients with giant basal cell carcinoma of the head and neck region underwent surgical excision and reconstruction at our hospital. Medical charts were retrospectively reviewed and analysed. The lesion was usually in the forehead, eyelid, lips or nasal-cheek region. The greatest diameter ranged from 5 to 11 cm, with 5-6 cm being the most common size at the time of presentation. All patients had their tumour resected and reconstructed in a single-stage procedure, mostly with a local advancement flap, and with no post-operative flap failure. Giant basal cell carcinoma of the head and neck can be successfully treated with a local flap in a single-stage approach.

  6. [Diffuse tenosenovial giant cell tumor of the wrist revealed by carpal tunnel syndrome: report of a case].

    PubMed

    Ait Essi, F; Younsi, A; Abkari, I; Benhima, M A; Najeb, Y; Latifi, M; Fakhri, A; Belaabidia, B

    2012-10-01

    Giant cell tumour of tendon sheath is a benign proliferative lesion of synovial origin that may affect the joints, bursae and tendon sheaths. It is the second most common soft tissue tumor of the hand after ganglion cyst. The localised (nodular) form is the most common. However, the less-common diffuse-type giant cell tumour is usually located in the peri-articular soft tissue. The authors report the case of a giant cell tumor of the tendon sheath arising from the carpal tunnel of the wrist in a 42-year-old woman. The patient presented a mild carpal tunnel syndrome and a mid-palmar swelling. We present an unusual localization of giant cell tumor of the tendon sheath, causing carpal tunnel syndrome. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  7. Denosumab: a new treatment option for giant cell tumor of bone.

    PubMed

    Lewin, J; Thomas, D

    2013-11-01

    Giant cell tumor of bone (GCTB) is an osteolytic, usually benign neoplasm characterized by infiltration with osteoclast-like giant cells, and the osteoclast differentiation factor receptor activator of nuclear factor kappa-B ligand (RANKL) is heavily involved in its pathogenesis. Denosumab belongs to a new class of drugs that inhibit RANKL. Prior to denosumab, multimodality treatment in refractory, recurrent and metastatic GCTB has shown variable results. Recent phase II data have demonstrated denosumab's activity with regard to disease and symptom control, without significant adverse effects. On the basis of this data, the FDA approved denosumab for the treatment of patients whose GCTB is unresectable, or when surgery is likely to result in severe morbidity. Ongoing questions remain, including the optimal scheduling, patient selection, use in the adjuvant setting and long-term toxicity concerns.

  8. [Joint replacement and giant-cell tumor. Report of 8 cases].

    PubMed

    Martínez-Estrada, J G; Santamaría-Bahena, O

    2016-01-01

    The giant-cell tumor is an aggressive neoplasia, represents approximately from the 5 the 8.6% of primary bone tumors; more of 50% affects the pelvic extremity, being able to affect the totality of the bones. To present the case series of tumors around the knee and hip that we offered a tumoral joint replacement as an alternative to amputation. We present eight cases of extensive giant cells tumors, we did en bloc resection and tumoral joint replacement. The clinical and radiological evolution was satisfactory, without postoperative complications and the most important, avoided an amputation with a better quality of life. Alternative reconstructive treatment option with a recovery to its normal life in a 80% and a low index of complications.

  9. CEMENTLESS ENDOPROSTHESIS IN THE TREATMENT OF GIANT CELL TUMOR OF THE TIBIA: EIGHTEEN YEARS OF EVOLUTION

    PubMed Central

    Mello, Glauco Pauka; Sonehara, Helio Ayabe; Neto, Mario Armani

    2015-01-01

    This is a case report on a giant cell tumor of the juxta-articular proximal tibia with a pathological fracture. A female patient presented pain and increased local volume after falling from her own height. She underwent clinical examination, radiographic examination and puncture biopsy. A diagnosis of giant cell tumor was made. The patient was then treated with tumor resection and use of an unconventional partial endoprosthesis of the tibia with preservation of the joint surface of the tibial plateau. The patient evolved with improvement of symptoms and maintenance of joint function of the operated limb, absence of recurrence and complications, without any need for reoperation over 18 years of follow-up. PMID:27026973

  10. Giant vesicles "colonies": a model for primitive cell communities.

    PubMed

    Carrara, Paolo; Stano, Pasquale; Luisi, Pier Luigi

    2012-07-09

    Current research on the origin of life typically focuses on the self-organisation of molecular components in individual cell-like compartments, thereby bringing about the emergence of self-sustaining minimal cells. This is justified by the fact that single cells are the minimal forms of life. No attempts have been made to investigate the cooperative mechanisms that could derive from the assembly of individual compartments. Here we present a novel experimental approach based on vesicles "colonies" as a model of primitive cell communities. Experiments show that several advantages could have favoured primitive cell colonies when compared with isolated primitive cells. In fact there are two novel unexpected features typical of vesicle colonies, namely solute capture and vesicle fusion, which can be seen as the basic physicochemical mechanisms at the origin of life.

  11. Giant cell tumor of the tendon sheath: a rare periungual location simulating myxoid cyst*

    PubMed Central

    Minotto, Renan; Rodrigues, Camila Britto; Grill, Aline Barcellos; Furian, Roque

    2017-01-01

    Giant cell tumor of the tendon sheath is a benign soft tissue tumor most frequent between the third and fifth decades of life. It can mimic and make differential diagnoses with several hand tumors. Definitive diagnosis and the treatment of choice are reached with complete resection and histopathological examination. Here we describe a case with clinical presentation similar to that of a myxoid cyst. PMID:28225971

  12. Autoimmune hemolytic anemia and giant cell hepatitis: Report of three infants.

    PubMed

    Ünal, Şule; Kuşkonmaz, Barış; Balamtekin, Necati; Baysoy, Gökhan; Aytaç Elmas, Selin; Orhan, Diclehan; Kale, Gülsev; Yüce, Aysel; Gürakan, Figen; Gümrük, Fatma; Çetin, Mualla

    2010-12-05

    Giant cell hepatitis associated with direct Coombs' test-positive hemolytic anemia is a rare condition of childhood and the pathogenesis remains unclear. An autoimmune activation and loss of self-tolerance in these patients may be the underlying pathology related to the response of some of the patients to immunosuppressive treatment. Herein, we report the clinical presentation and course of three consecutive patients with this rare condition. We conclude that serum ferritin at diagnosis may be used for prediction of the outcome.

  13. The Peripheral Giant Cell Granuloma in Edentulous Patients: Report of Three Unique Cases

    PubMed Central

    Etoz, Osman A.; Demirbas, Ahmet Emin; Bulbul, Mehmet; Akay, Ebru

    2010-01-01

    The peripheral giant cell granuloma (PGCG) is a rare reactive exophytic lesion taking place on the gingiva and alveolar ridge usually as a result of local irritating factors such as trauma, tooth extraction, badly finished fillings, unstable dental prosthesis, plaque, calculus, chronic infections, and impacted food. This article presents 3 cases of PGCG that presented at the same location of the edentulous mandible of patients that using complete denture for over ten years. PMID:20613923

  14. Primary giant cell malignant fibrous histiocytoma-associated with renal calculus

    PubMed Central

    Altunkol, Adem; Savas, Murat; Ciftci, Halil; Gulum, Mehmet; Yagmur, Ismail; Bitiren, Muharrem

    2014-01-01

    Malignant fibrous histiocytomas (MFH) are the most commonly seen soft tissue sarcomas in adults. It is rarely seen in some visceral organs. Kidneys are the parenchymal organs in which MFHs are most frequently seen. More than 50 cases of primary renal MFH have been reported. Among these cases, only 1 was reported as primary giant cell subtype in association with urolithiasis. This case report is the second such case with the these characteristics. PMID:24678364

  15. Primary hyperparathyroidism associated with a giant cell tumor: One case in the distal radius.

    PubMed

    Ouzaa, M R; Bennis, A; Iken, M; Abouzzahir, A; Boussouga, M; Jaafar, A

    2015-10-01

    Hyperparathyroidism can present itself as brown tumors (or osteolytic expansive lesions) that usually disappear after normalization of calcium and phosphate levels. It rarely occurs simultaneously with a giant cell tumor. The authors report one case of a localized form at the distal radius in a patient being followed for primary hyperparathyroidism. The diagnostic challenges related to the clinical and radiological similarities of these two pathological entities are discussed, as they can lead to delays in therapeutic management.

  16. Melorheostosis and central giant cell granuloma of the mandible in a 15-year-old girl.

    PubMed

    Anderson, K M; Shintaku, W H; Rosebush, M S; Rawal, Y B; Woodard, E S

    2013-11-01

    Melorheostosis is a nonhereditary bone dysplasia primarily affecting the appendicular skeleton. Because clinical and histologic features are often nonspecific, the diagnosis is often based on the radiographic presentation. Involvement of the craniofacial skeleton is rare. We describe a case of a 15-year-old girl with appendicular and craniofacial melorheostosis with adjacent central giant cell granuloma. We discuss the possible significance of this previously unreported finding. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Tocilizumab for giant cell arteritis with corticosteroid-resistant progressive anterior ischemic optic neuropathy.

    PubMed

    Vionnet, Julien; Buss, Guillaume; Mayer, Cédric; Sokolov, Arseny A; Borruat, François-Xavier; Spertini, François

    2017-10-01

    Giant cell arteritis is an inflammatory disorder of the medium- and large-size arteries. Permanent visual loss related to arteritic anterior ischemic optic neuropathy is among the most serious complications of this disease and initial treatment usually consists of high dose corticosteroids. There is no consensus in the literature concerning the optimal therapeutic approach in giant cell arteritis patients with corticosteroid-resistant arteritic anterior ischemic optic neuropathy. A 73-year-old Caucasian female with biopsy-proven giant cell arteritis developed an acute visual loss of the right eye due to arteritic anterior ischemic optic neuropathy. Despite 5 daily methylprednisolone pulses, systemic symptoms persisted and rapid involvement of the controlateral eye was documented. Therefore, tocilizumab (humanised monoclonal antibody binding the human interleukin-6 receptor) was introduced as a potential salvage therapy with a swift consecutive resolution of the systemic symptoms and stabilization of the ophthalmic lesions. Although a late effect of steroids pulses cannot be formally ruled out in this dramatic situation, tocilizumab likely offered a decisive effect in preventing bilateral blindness and may have contributed to steroid tapering. Tocilizumab may represent a new early effective second-line treatment option in corticosteroid-resistant anterior ischemic optic neuropathy. More data are needed to confirm this observation and to evaluate the safety profile of this treatment. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  18. Giant cell tumor: rapid recurrence after cessation of long-term denosumab therapy.

    PubMed

    Matcuk, George R; Patel, Dakshesh B; Schein, Aaron J; White, Eric A; Menendez, Lawrence R

    2015-07-01

    We report a case of rapid recurrence of a giant cell tumor (GCT) of the distal radius in a 24-year-old woman following the cessation of long-term denosumab therapy. GCT of bone is a histologically benign tumor with multinucleated giant cells on a background of mononuclear giant cells usually presenting as a well-defined epi-metaphyseal lytic lesion without sclerotic margins. Denosumab, a monoclonal antibody to the receptor activator of nuclear factor kappa-B ligand (RANKL), has proven to be an effective neoadjuvant treatment for GCT. The tumor in this case had demonstrated a good response with sustained control for over 2 years while on denosumab therapy. However, within 2 months of cessation of therapy, the tumor demonstrated rapid recurrence and progression with growth, osteolysis, and increased soft tissue component. Despite reinitiating denosumab therapy, there was progressive tumor growth and destruction, ultimately necessitating below-the-elbow amputation. This case illustrates the need for maintenance of denosumab therapy for GCT of bone or definitive surgical treatment prior to its cessation.

  19. [Giant cell arteritis with eye involvment--color Doppler imaging or retrobulabar vessels findings].

    PubMed

    Jianu, Silviana Nina; Jianu, D C

    2010-01-01

    Giant cell arteritis (temporal arteritis) is a primary vasculitis, that affects large arteries, especially branches of the external carotid artery (ECA). To assess the role of CDI of retrobulbar vessels in the study of two patients with giant cell arteritis with eye involvement. We have used a sonographer with 8-15 MHz linear probe. Both patients presented malaise, temporal headache, tender temporal arteries and signs of inflammation. The first patient had a central retinal artery obstruction of the right eye, and the second had anterior ischaemic optic neuropathy of the left eye. Temporal artery histology was positive in both cases. Ultrasound investigation was performed within the first 10 days of corticosteroid treatment. CDI of retrobulbar vessels detected low blood velocities, especially end-diastolic velocities and high resistance index in all retrobulbar vessels, in both orbits. Typical sonographic features in temporal arteritis were "halo", associated with stenoses or occlusions of branches of ECA. Ultrasound investigation is a valuable diagnostic tool to investigate giant cell arteritis.

  20. The role of color duplex sonography in the diagnosis of giant cell arteritis.

    PubMed

    Romera-Villegas, Antonio; Vila-Coll, Ramón; Poca-Dias, Violant; Cairols-Castellote, Marc A

    2004-11-01

    To determine the clinical usefulness of color duplex sonography in the diagnosis of giant cell arteritis as an alternative to temporal artery biopsy. From May 1998 to November 2002, 68 consecutive patients seen in our hospital with a clinical suggestion of active temporal arteritis were included. Forty-eight patients were female and 20 were male, with a mean age of 77 years. Color duplex sonography with a linear array transducer (5-10 MHz) was used to assess temporal artery morphologic characteristics before a biopsy was performed. The main sonographic criterion for a positive diagnosis was visualization of a hypoechoic halo around the temporal artery. These data were compared with pathologic findings. The kappa statistic was used to determine the level of agreement. Sensitivity, specificity, positive and negative predictive values, and accuracy of duplex sonography as a diagnostic test were assessed. The color duplex sonographic findings were positive in 25 of 68 patients with a clinical suggestion of giant cell arteritis. The diagnosis was confirmed by biopsy in 22 patients; there were 4 false-positive results and 1 false-negative result by duplex sonography. The kappa value was 0.84. Sensitivity, specificity, positive and negative predictive values, and accuracy for duplex sonography were 95.4%, 91.3%, 84%, 97.6%, and 92.6%, respectively. The use of high-resolution color duplex sonography may replace biopsy in the diagnosis of giant cell arteritis.

  1. Garcin syndrome resulting from a giant cell tumor of the skull base in a child.

    PubMed

    Bibas-Bonet, Hilda; Fauze, Ricardo A; Lavado, María Graciela; Páez, Rafael O; Nieman, Judith

    2003-05-01

    Garcin syndrome is characterized by a progressive ipsilateral involvement of cranial nerves, culminating in paralysis of all or at least seven of them, without sensory or motor long-tract disturbance, with no intracranial hypertension, and with osteoclastic involvement in the skull base on radiographic computed tomography. Giant cell tumor is a primary bone tumor rarely affecting the skull base. An 8-year-old female presented with a 3-month history of increasingly worsening right otalgia, tinnitus, hearing loss, right facial numbness, and diplopia. She was admitted with a 2-week history of swallowing difficulties, voice change, and right shoulder pain. Neurologic examination disclosed unilateral paralysis of the right fifth through twelfth cranial nerves, with no other abnormal neurologic findings. Skull radiographic computed tomography revealed lytic lesions in the right temporal petrous portion. Computed tomographic scan indicated a destructive mass involving the right greater wing of the sphenoid bone and temporal petrous apex. Magnetic resonance imaging demonstrated a tumor arising from the temporosphenoidal region, infiltrating neither the brain nor the brainstem. No hydrocephalus was observed. Biopsy revealed giant cell tumor. Posterior treatment consisted of radiotherapy. At an 8-year follow-up, the patient was well but with functional sequelae. There is no magnetic resonance imaging evidence of tumor growth. No other giant cell tumor presenting as Garcin syndrome is known to have been reported.

  2. Soft Tissue Giant Cell Tumour of Low Malignant Potential: A Rare Tumour at a Rare Site

    PubMed Central

    Bhat, Amoolya; V., Geethamani; C., Vijaya

    2013-01-01

    “Soft tissue giant cell tumour of low malignant potential” is considered as the soft tissue counterpart of osteoclastoma of the bone. It is a primary soft tissue tumour which is classified under the category of fibrohistiocytic tumours of intermediate malignancy.Seventy percent of the tumours involve the extremities and only about seven percent of them arise in head and neck region. They are composed of nodules of histiocytes in a vascular stroma, with multinucleated osteoclast-like giant cells positive for vimentin, smooth muscle actin (SMA), CD68 and Tarterate Resistant Acid Phosphatase (TRAP). We are presenting a case of a 75-year-old man who had a nodule on the ala of the nose. Histopathology showed a histiocytic lesion. Benign fibrous histiocytoma, plexiform fibrohistiocytic tumour, solitary reticulohistiocytoma and histioid leprosy were ruled out by using special stains and immunostains. Expression of smooth muscle actin and CD68 confirmed the diagnosis of a soft tissue giant cell tumour with a low malignant potential. PMID:24551690

  3. Two Cases of Sarcoma Arising in Giant Cell Tumor of Bone Treated with Denosumab

    PubMed Central

    Broehm, Cory Julian; Garbrecht, Erika L.; Wood, Jeff; Bocklage, Therese

    2015-01-01

    Giant cell tumor (GCT) of bone is a generally benign, but often locally aggressive, neoplasm of bone, with a propensity for recurrence. Sarcomatous transformation is rare and typically occurs with a history of recurrences and radiation treatment. Denosumab, an inhibitor of the RANK ligand involved in bone resorption in GCT, is increasingly used in treatment of recurrent or unresectable giant cell tumor of bone. We report two cases of sarcomatous transformation of GCT to osteosarcoma in patients receiving denosumab. One was a 59-year-old male with a 12-year history of GCT and multiple recurrences taking denosumab for 2.5 years. The second case was in a 56-year-old male with a seven-year history of GCT taking denosumab for six months. Review of the literature shows one case report of malignant transformation of GCT in a patient being treated with denosumab. As the use of denosumab for treatment of GCT will likely increase, larger, controlled studies are needed to ascertain whether denosumab may play a role in malignant transformation of giant cell tumor of bone. PMID:26798348

  4. Signature of clustering in quantum many-body systems probed by the giant dipole resonance

    NASA Astrophysics Data System (ADS)

    Pandit, Deepak; Mondal, Debasish; Dey, Balaram; Bhattacharya, Srijit; Mukhopadhyay, S.; Pal, Surajit; De, A.; Banerjee, S. R.

    2017-03-01

    The present experimental study illustrates how large deformations attained by nuclei due to cluster formation are perceived through the giant dipole resonance (GDR) strength function. The high energy GDR γ rays have been measured from 32S at different angular momenta (J ) but similar temperatures in the reactions 4He(Elab=45 MeV )+28Si and 20Ne(Elab=145 MeV )+12C . The experimental data at lower J (˜10 ℏ ) suggests a normal deformation, similar to the ground state value, showing no potential signature of clustering. However, it is found that the GDR lineshape is fragmented into two prominent peaks at high J (˜20 ℏ ) providing a direct measurement of the large deformation developed in the nucleus. The observed lineshape is also completely different from the ones seen for Jacobi shape transition at high J pointing towards the formation of cluster structure in superdeformed states of 32S at such high spin. Thus, the GDR can be regarded as a unique tool to study cluster formation at high excitation energies and angular momenta.

  5. The burden of subependymal giant cell astrocytomas associated with tuberous sclerosis complex: results of a patient and caregiver survey.

    PubMed

    Skalicky, Anne M; Rentz, Anne M; Liu, Zhimei; Wheless, James W; Pelletier, Corey L; Dunn, David W; Frost, Michael D; Nakagawa, JoAnne; Magestro, Matthew; Prestifilippo, Judith; Pashos, Chris

    2015-04-01

    Tuberous sclerosis complex is a genetic disorder characterized by benign tumor growth including lesions in the ventricular system of the brain known as subependymal giant cell astrocytomas. This analysis focuses on the clinical presentation, management, and associated burden of subependymal giant cell astrocytomas in patients with tuberous sclerosis complex in the United States. An institutional review board-approved web-based survey of tuberous sclerosis complex patients and caregivers collected information, and descriptive analyses were conducted on age-based subgroups. A total of 116 tuberous sclerosis complex-subependymal giant cell astrocytoma patients or caregivers responded (17% of the total tuberous sclerosis complex sample). Mean and median patient ages were 25.5 and 23.5 years. Besides subependymal giant cell astrocytomas, patients also experienced skin lesions (72%), seizures (65%), and cognitive concerns (60%). Forty-five percent reported having brain surgery (22% for subependymal giant cell astrocytoma). In the past year, 42% of patients were admitted at least once to the hospital whereas 39% went to the emergency department. Results demonstrate that tuberous sclerosis complex-subependymal giant cell astrocytoma is associated with significant clinical burden, resource utilization, and decreased well-being. © The Author(s) 2014.

  6. MAP65-3 Microtubule-Associated Protein Is Essential for Nematode-Induced Giant Cell Ontogenesis in Arabidopsis[W

    PubMed Central

    Caillaud, Marie-Cécile; Lecomte, Philippe; Jammes, Fabien; Quentin, Michaël; Pagnotta, Sophie; Andrio, Emilie; de Almeida Engler, Janice; Marfaing, Nicolas; Gounon, Pierre; Abad, Pierre; Favery, Bruno

    2008-01-01

    The infection of plants by obligate parasitic nematodes constitutes an interesting model for investigating plant cytoskeleton functions. Root knot nematodes have evolved the ability to manipulate host functions to their own advantage by redifferentiating root cells into multinucleate and hypertrophied feeding cells. These giant cells result from repeated rounds of karyokinesis without cell division. Detailed functional analyses demonstrated that Arabidopsis thaliana Microtubule-Associated Protein65-3 (MAP65-3) was essential for giant cell ontogenesis and that cytokinesis was initiated but not completed in giant cells. In developing giant cells, MAP65-3 was associated with a novel kind of cell plate—the giant cell mini cell plate—that separates daughter nuclei. In the absence of functional MAP65-3, giant cells developed but failed to fully differentiate and were eventually destroyed. These defects in giant cells impaired the maturation of nematode larvae. Thus, MAP65-3 is essential for giant cell development during root knot nematode infection. Subcellular localization of MAP65-3 and analysis of microtubule organization in the dyc283 T-DNA map65-3 mutant demonstrated that MAP65-3 played a critical role in organizing the mitotic microtubule array during both early and late mitosis in all plant organs. Here, we propose a model for the role of MAP65-3 in giant cell ontogenesis. PMID:18263774

  7. Application of Nuclear Volume Measurements to Comprehend the Cell Cycle in Root-Knot Nematode-Induced Giant Cells

    PubMed Central

    Antonino de Souza Junior, José Dijair; Pierre, Olivier; Coelho, Roberta R.; Grossi-de-Sa, Maria F.; Engler, Gilbert; de Almeida Engler, Janice

    2017-01-01

    Root-knot nematodes induce galls that contain giant-feeding cells harboring multiple enlarged nuclei within the roots of host plants. It is recognized that the cell cycle plays an essential role in the set-up of a peculiar nuclear organization that seemingly steers nematode feeding site induction and development. Functional studies of a large set of cell cycle genes in transgenic lines of the model host Arabidopsis thaliana have contributed to better understand the role of the cell cycle components and their implication in the establishment of functional galls. Mitotic activity mainly occurs during the initial stages of gall development and is followed by an intense endoreduplication phase imperative to produce giant-feeding cells, essential to form vigorous galls. Transgenic lines overexpressing particular cell cycle genes can provoke severe nuclei phenotype changes mainly at later stages of feeding site development. This can result in chaotic nuclear phenotypes affecting their volume. These aberrant nuclear organizations are hampering gall development and nematode maturation. Herein we report on two nuclear volume assessment methods which provide information on the complex changes occurring in nuclei during giant cell development. Although we observed that the data obtained with AMIRA tend to be more detailed than Volumest (Image J), both approaches proved to be highly versatile, allowing to access 3D morphological changes in nuclei of complex tissues and organs. The protocol presented here is based on standard confocal optical sectioning and 3-D image analysis and can be applied to study any volume and shape of cellular organelles in various complex biological specimens. Our results suggest that an increase in giant cell nuclear volume is not solely linked to increasing ploidy levels, but might result from the accumulation of mitotic defects. PMID:28659939

  8. Giant Cell Tumor of Bone With Pseudosarcomatous Changes Leading to Premature Denosumab Therapy Interruption: A Case Report With Review of the Literature.

    PubMed

    Sanchez-Pareja, Andrea; Larousserie, Frédérique; Boudabbous, Sana; Beaulieu, Jean-Yves; Mach, Nicolas; Saiji, Essia; Rougemont, Anne-Laure

    2016-06-01

    Denosumab has shown promising results in the management of giant cell tumor of bone, a primary bone tumor with locally aggressive behaviour. We report a case of premature denosumab interruption due to radiological and clinical tumor expansion of a giant cell tumor of the distal ulna. Although denosumab is known to induce tumor regression, with progressive ossification and loss of the characteristic morphology of giant cell tumor of bone, the ulnar tumor specimen showed a moderately to highly cellular proliferation of short spindle-shaped cells, and no osteoclast-like giant cells. There were no abnormal mitotic figures. We considered the surgical specimen as a giant cell tumor of bone with partial regression after prematurely interrupted denosumab treatment. This case illustrates the diagnostic issues of an initially unfavourable evolution raising concern for malignancy, and the difficulties in histological assessment of a partially treated giant cell tumor of bone, that may mimic osteosarcoma.

  9. Giant Mediastinal Germ Cell Tumour: An Enigma of Surgical Consideration

    PubMed Central

    Ali, Nurayub Mohd; Azizan, Nornazirah; Zakaria, Andee Dzulkarnaen; Rahman, Mohd Ramzisham Abdul

    2016-01-01

    We present a case of 16-year-old male, who was referred from private centre for dyspnoea, fatigue, and orthopnea. The chest radiograph revealed complete opacification of left chest which was confirmed by computed tomography as a large left mediastinal mass measuring 14 × 15 × 18 cm. The diagnostic needle core biopsy revealed mixed germ cell tumour with possible combination of embryonal carcinoma, yolk sac, and teratoma. After 4 cycles of neoadjuvant BEP regime, there was initial response of tumour markers but not tumour bulk. Instead of classic median sternotomy or clamshell incision, posterolateral approach with piecemeal manner was chosen. Histology confirmed mixed germ cell tumour with residual teratomatous component without yolk sac or embryonal carcinoma component. Weighing 3.5 kg, it is one of the largest mediastinal germ cell tumours ever reported. We describe this rare and gigantic intrathoracic tumour and discuss the spectrum of surgical approach and treatment of this exceptional tumour. PMID:27807495

  10. Differentiation of trophoblast giant cells and their metabolic functions are dependent on peroxisome proliferator-activated receptor beta/delta.

    PubMed

    Nadra, Karim; Anghel, Silvia I; Joye, Elisabeth; Tan, Nguan Soon; Basu-Modak, Sharmila; Trono, Didier; Wahli, Walter; Desvergne, Béatrice

    2006-04-01

    Mutation of the nuclear receptor peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) severely affects placenta development, leading to embryonic death at embryonic day 9.5 (E9.5) to E10.5 of most, but not all, PPARbeta/delta-null mutant embryos. While very little is known at present about the pathway governed by PPARbeta/delta in the developing placenta, this paper demonstrates that the main alteration of the placenta of PPARbeta/delta-null embryos is found in the giant cell layer. PPARbeta/delta activity is in fact essential for the differentiation of the Rcho-1 cells in giant cells, as shown by the severe inhibition of differentiation once PPARbeta/delta is silenced. Conversely, exposure of Rcho-1 cells to a PPARbeta/delta agonist triggers a massive differentiation via increased expression of 3-phosphoinositide-dependent kinase 1 and integrin-linked kinase and subsequent phosphorylation of Akt. The links between PPARbeta/delta activity in giant cells and its role on Akt activity are further strengthened by the remarkable pattern of phospho-Akt expression in vivo at E9.5, specifically in the nucleus of the giant cells. In addition to this phosphatidylinositol 3-kinase/Akt main pathway, PPARbeta/delta also induced giant cell differentiation via increased expression of I-mfa, an inhibitor of Mash-2 activity. Finally, giant cell differentiation at E9.5 is accompanied by a PPARbeta/delta-dependent accumulation of lipid droplets and an increased expression of the adipose differentiation-related protein (also called adipophilin), which may participate to lipid metabolism and/or steroidogenesis. Altogether, this important role of PPARbeta/delta in placenta development and giant cell differentiation should be considered when contemplating the potency of PPARbeta/delta agonist as therapeutic agents of broad application.

  11. Establishment of three cell lines from Chinese giant salamander and their sensitivities to the wild-type and recombinant ranavirus.

    PubMed

    Yuan, Jiang-Di; Chen, Zhong-Yuan; Huang, Xing; Gao, Xiao-Chan; Zhang, Qi-Ya

    2015-06-12

    Known as lethal pathogens, Ranaviruses have been identified in diseased fish, amphibians (including Chinese giant salamander Andrias davidianus, the world's largest amphibian) and reptiles, causing organ necrosis and systemic hemorrhage. Here, three Chinese giant salamander cell lines, thymus cell line (GSTC), spleen cell line (GSSC) and kidney cell line (GSKC) were initially established. Their sensitivities to ranaviruses, wild-type Andrias davidianus ranavirus (ADRV) and recombinant Rana grylio virus carrying EGFP gene (rRGV-EGFP) were tested. Temporal transcription pattern of ranavirus major capsid protein (MCP), fluorescence and electron microscopy observations showed that both the wild-type and recombinant ranavirus could replicate in the cell lines.

  12. A giant benign clear cell hidradenoma on the anterior trunk.

    PubMed

    Demirci, Gulsen Tukenmez; Atis, Guldehan; Altunay, Ilknur Kivanç; Sakiz, Damlanur

    2011-10-05

    Clear cell hidradenoma (CCH) is an uncommon variant of benign cutaneous adnexal tumors. These tumors are clinically asymptomatic, solitary dermal nodules. They occur most frequently on the scalp, face abdomen and extremities. Growth is slow and malignant change is rare. 45-year-old woman presented with a nodule which had begun 4 years ago as a small nodular asymptomatic lesion and had a central ulceration and a minimal hemorrhagic discharge on her anterior abdomen wall. On dermatologic examination there was a 6.5×5×4 cm non-tender, soft reddish purple nodule, with lobular appearance and ulceration. In the laboratory investigations, all hematologic and biochemical tests were normal. A computed tomography (CT) scan demonstrated a cystic tumor with lobulated contour with contrast enhancement. The lesion was excised totally. In histopathological examination, the tumor was composed of biphasic smaller dark polygonal cells and larger clear cells and coarse nuclear chromatine. There were duct like structures. Immunohistochemical investigation was done for the suspicion of malignancy. Cytoplasm of clear cells and of duct like structures showed PAS-positive and d-PAS resistant staining. There was a positive reaction to epithelial membrane antigen and carcinoembryonic antigen. The mitotic index in Ki 67 examination was low. All these findings confirmed the diagnosis of benign CCH.

  13. A short-term in vivo model for giant cell tumor of bone

    PubMed Central

    2011-01-01

    Background Because of the lack of suitable in vivo models of giant cell tumor of bone (GCT), little is known about its underlying fundamental pro-tumoral events, such as tumor growth, invasion, angiogenesis and metastasis. There is no existing cell line that contains all the cell and tissue tumor components of GCT and thus in vitro testing of anti-tumor agents on GCT is not possible. In this study we have characterized a new method of growing a GCT tumor on a chick chorio-allantoic membrane (CAM) for this purpose. Methods Fresh tumor tissue was obtained from 10 patients and homogenized. The suspension was grafted onto the CAM at day 10 of development. The growth process was monitored by daily observation and photo documentation using in vivo biomicroscopy. After 6 days, samples were fixed and further analyzed using standard histology (hematoxylin and eosin stains), Ki67 staining and fluorescence in situ hybridization (FISH). Results The suspension of all 10 patients formed solid tumors when grafted on the CAM. In vivo microscopy and standard histology revealed a rich vascularization of the tumors. The tumors were composed of the typical components of GCT, including (CD51+/CD68+) multinucleated giant cells whichwere generally less numerous and contained fewer nuclei than in the original tumors. Ki67 staining revealed a very low proliferation rate. The FISH demonstrated that the tumors were composed of human cells interspersed with chick-derived capillaries. Conclusions A reliable protocol for grafting of human GCT onto the chick chorio-allantoic membrane is established. This is the first in vivo model for giant cell tumors of bone which opens new perspectives to study this disease and to test new therapeutical agents. PMID:21668953

  14. Giant cell interstitial pneumonia in patients without hard metal exposure: analysis of 3 cases and review of the literature.

    PubMed

    Khoor, Andras; Roden, Anja C; Colby, Thomas V; Roggli, Victor L; Elrefaei, Mohamed; Alvarez, Francisco; Erasmus, David B; Mallea, Jorge M; Murray, David L; Keller, Cesar A

    2016-04-01

    Giant cell interstitial pneumonia is a rare lung disease and is considered pathognomonic for hard metal lung disease, although some cases with no apparent hard metal (tungsten carbide cobalt) exposure have been reported. We aimed to explore the association between giant cell interstitial pneumonia and hard metal exposure. Surgical pathology files from 2001 to 2004 were searched for explanted lungs with the histopathologic diagnosis of giant cell interstitial pneumonia, and we reviewed the associated clinical histories. Mass spectrometry, energy-dispersive x-ray analysis, and human leukocyte antigen typing data were evaluated. Of the 455 lung transplants, 3 met the histologic criteria for giant cell interstitial pneumonia. Patient 1 was a 36-year-old firefighter, patient 2 was a 58-year-old welder, and patient 3 was a 45-year-old environmental inspector. None reported exposure to hard metal or cobalt dust. Patients 1 and 2 received double lung transplants; patient 3 received a left single-lung transplant. Histologically, giant cell interstitial pneumonia presented as chronic interstitial pneumonia with fibrosis, alveolar macrophage accumulation, and multinucleated giant cells of both alveolar macrophage and type 2 cell origin. Energy-dispersive x-ray analysis revealed no cobalt or tungsten particles in samples from the explanted lungs. None of the samples had detectable tungsten levels, and only patient 2 had elevated cobalt levels. The lack of appropriate inhalation history and negative analytical findings in the tissue from 2 of the 3 patients suggests that giant cell interstitial pneumonia is not limited to individuals with hard metal exposure, and other environmental factors may elicit the same histologic reaction.

  15. Senile macular degeneration. The involvement of giant cells in atrophy of the retinal pigment epithelium.

    PubMed

    Penfold, P L; Killingsworth, M C; Sarks, S H

    1986-03-01

    Senile macular degeneration (SMD) is a leading cause of registered blindness in the United States and other Western countries. Loss of central vision develops as a result of atrophy of the retinal pigment epithelium or subretinal neovascularisation. The histopathology of the atrophic form of SMD has not been extensively studied. This paper illustrates at the light and electron microscope level the involvement the atrophic form of SMD. Additional features including pigment clumping and detachment of the retinal pigment epithelium at the advancing edge of the lesion are illustrated. Giant cells and MPS cells are typical features of granulomatous inflammation, and results suggest that they may play a role in the pathogenesis of SMD.

  16. Apoptosis triggered by pyropheophorbide-α methyl ester-mediated photodynamic therapy in a giant cell tumor in bone

    NASA Astrophysics Data System (ADS)

    Li, K.-T.; Zhang, J.; Duan, Q.-Q.; Bi, Y.; Bai, D.-Q.; Ou, Y.-S.

    2014-06-01

    A giant cell tumor in bone is the common primary bone tumor with aggressive features, occurring mainly in young adults. Photodynamic therapy is a new therapeutic technique for tumors. In this study, we investigated the effects of Pyropheophorbide-α methyl ester (MPPa)-mediated photodynamic therapy on the proliferation of giant cell tumor cells and its mechanism of action. Cell proliferation was evaluated using an MTT assay. Cellular apoptosis was detected by Hoechst nuclear staining, and flow cytometric assay. Mitochondrial membrane potential changes and cytochrome c, caspase-9, caspase-3, and Bcl-2 expression was assessed. Finally, we found that MPPa-mediated photodynamic therapy could effectively suppress the proliferation of human giant cell tumor cells and induce apoptosis. The mitochondrial pathway was involved in the MPPa-photodynamic therapy-induced apoptosis.

  17. Giant Lysosomes as a Chemotherapy Resistance Mechanism in Hepatocellular Carcinoma Cells

    PubMed Central

    Colombo, Federico; Trombetta, Elena; Cetrangolo, Paola; Maggioni, Marco; Razini, Paola; De Santis, Francesca; Torrente, Yvan; Prati, Daniele; Torresani, Erminio; Porretti, Laura

    2014-01-01

    Despite continuous improvements in therapeutic protocols, cancer-related mortality is still one of the main problems facing public health. The main cause of treatment failure is multi-drug resistance (MDR: simultaneous insensitivity to different anti-cancer agents), the underlying molecular and biological mechanisms of which include the activity of ATP binding cassette (ABC) proteins and drug compartmentalisation in cell organelles. We investigated the expression of the main ABC proteins and the role of cytoplasmic vacuoles in the MDR of six hepatocellular carcinoma (HCC) cell lines, and confirmed the accumulation of the yellow anti-cancer drug sunitinib in giant (four lines) and small cytoplasmic vacuoles of lysosomal origin (two lines). ABC expression analyses showed that the main ABC protein harboured by all of the cell lines was PGP, whose expression was not limited to the cell membrane but was also found on lysosomes. MTT assays showed that the cell lines with giant lysosomes were more resistant to sorafenib treatment than those with small lysosomes (p<0.01), and that verapamil incubation can revert this resistance, especially if it is administered after drug pre-incubation. The findings of this study demonstrate the involvement of PGP-positive lysosomes in drug sequestration and MDR in HCC cell lines. The possibility of modulating this mechanism using PGP inhibitors could lead to the development of new targeted strategies to enhance HCC treatment. PMID:25493932

  18. Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

    PubMed Central

    2013-01-01

    Phosphoinositides (PIs) make up only a small fraction of cellular phospholipids, yet they control almost all aspects of a cell's life and death. These lipids gained tremendous research interest as plasma membrane signaling molecules when discovered in the 1970s and 1980s. Research in the last 15 years has added a wide range of biological processes regulated by PIs, turning these lipids into one of the most universal signaling entities in eukaryotic cells. PIs control organelle biology by regulating vesicular trafficking, but they also modulate lipid distribution and metabolism via their close relationship with lipid transfer proteins. PIs regulate ion channels, pumps, and transporters and control both endocytic and exocytic processes. The nuclear phosphoinositides have grown from being an epiphenomenon to a research area of its own. As expected from such pleiotropic regulators, derangements of phosphoinositide metabolism are responsible for a number of human diseases ranging from rare genetic disorders to the most common ones such as cancer, obesity, and diabetes. Moreover, it is increasingly evident that a number of infectious agents hijack the PI regulatory systems of host cells for their intracellular movements, replication, and assembly. As a result, PI converting enzymes began to be noticed by pharmaceutical companies as potential therapeutic targets. This review is an attempt to give an overview of this enormous research field focusing on major developments in diverse areas of basic science linked to cellular physiology and disease. PMID:23899561

  19. Tiny solar cells may sprout a giant for Texas Instruments

    SciTech Connect

    Best, D.

    1982-07-01

    The Texas Instruments solar energy system is described. The closed-loop system consists of 4 main components: (1) the solar chemical converter; (2) hydrogen storage; (3) fuel cell; and (4) heat exchanger. The solar chemical converter contains thousands of tiny, spherical, single-crystal photovoltaic (PV) cells embedded in a glass matrix with a conductive backing. Sunlight-to-electricity conversion efficiency is 13%. Operation of the system is described as follows: when sunlight is available, the electricity generated by the PV sheet in the solar chemical converter is used to electrolyze HBr into H/sub 2/ and Br/sub 2/. The hydrogen is stored in one part of the system while the hot Br/sub 2/ is cycled to the heat storage and heat exchanger unit. Electricity is produced by combining the H/sub 2/ and Br/sub 2/ in the fuel cell; thermal energy is obtained from the heat storage and heat exchanger unit. Advantages of this system (expected to provide 90% of a home's power) are discussed and current status of the project is reviewed. (MJJ)

  20. The extinct, giant giraffid Sivatherium giganteum: skeletal reconstruction and body mass estimation.

    PubMed

    Basu, Christopher; Falkingham, Peter L; Hutchinson, John R

    2016-01-01

    Sivatherium giganteum is an extinct giraffid from the Plio-Pleistocene boundary of the Himalayan foothills. To date, there has been no rigorous skeletal reconstruction of this unusual mammal. Historical and contemporary accounts anecdotally state that Sivatherium rivalled the African elephant in terms of its body mass, but this statement has never been tested. Here, we present a three-dimensional composite skeletal reconstruction and calculate a representative body mass estimate for this species using a volumetric method. We find that the estimated adult body mass of 1246 kg (857-1812 kg range) does not approach that of an African elephant, but confirms that Sivatherium was certainly a large giraffid, and may have been the largest ruminant mammal that has ever existed. We contrast this volumetric estimate with a bivariate scaling estimate derived from Sivatherium's humeral circumference and find that there is a discrepancy between the two. The difference implies that the humeral circumference of Sivatherium is greater than expected for an animal of this size, and we speculate this may be linked to a cranial shift in centre of mass. © 2016 The Authors.

  1. The extinct, giant giraffid Sivatherium giganteum: skeletal reconstruction and body mass estimation

    PubMed Central

    2016-01-01

    Sivatherium giganteum is an extinct giraffid from the Plio–Pleistocene boundary of the Himalayan foothills. To date, there has been no rigorous skeletal reconstruction of this unusual mammal. Historical and contemporary accounts anecdotally state that Sivatherium rivalled the African elephant in terms of its body mass, but this statement has never been tested. Here, we present a three-dimensional composite skeletal reconstruction and calculate a representative body mass estimate for this species using a volumetric method. We find that the estimated adult body mass of 1246 kg (857—1812 kg range) does not approach that of an African elephant, but confirms that Sivatherium was certainly a large giraffid, and may have been the largest ruminant mammal that has ever existed. We contrast this volumetric estimate with a bivariate scaling estimate derived from Sivatherium's humeral circumference and find that there is a discrepancy between the two. The difference implies that the humeral circumference of Sivatherium is greater than expected for an animal of this size, and we speculate this may be linked to a cranial shift in centre of mass. PMID:26763212

  2. A NEW HYBRID N-BODY-COAGULATION CODE FOR THE FORMATION OF GAS GIANT PLANETS

    SciTech Connect

    Bromley, Benjamin C.; Kenyon, Scott J. E-mail: skenyon@cfa.harvard.edu

    2011-04-20

    We describe an updated version of our hybrid N-body-coagulation code for planet formation. In addition to the features of our 2006-2008 code, our treatment now includes algorithms for the one-dimensional evolution of the viscous disk, the accretion of small particles in planetary atmospheres, gas accretion onto massive cores, and the response of N-bodies to the gravitational potential of the gaseous disk and the swarm of planetesimals. To validate the N-body portion of the algorithm, we use a battery of tests in planetary dynamics. As a first application of the complete code, we consider the evolution of Pluto-mass planetesimals in a swarm of 0.1-1 cm pebbles. In a typical evolution time of 1-3 Myr, our calculations transform 0.01-0.1 M{sub sun} disks of gas and dust into planetary systems containing super-Earths, Saturns, and Jupiters. Low-mass planets form more often than massive planets; disks with smaller {alpha} form more massive planets than disks with larger {alpha}. For Jupiter-mass planets, masses of solid cores are 10-100 M{sub +}.

  3. Giant cell tumor of bone with secondary aneurysmal bone cyst-like change producing β-human chorionic gonadotropin.

    PubMed

    Fitzhugh, Valerie A; Katava, Gordana; Wenokor, Cornelia; Roche, Natalie; Beebe, Kathleen S

    2014-06-01

    Giant cell tumor of bone is a benign, locally aggressive neoplasm that is composed of sheets of neoplastic mononuclear cells interspersed amongst non-neoplastic, uniformly distributed, osteoclast-like giant cells. They represent approximately 4-5% of primary bone tumors. Rarely, bone tumors have been noted to produce human chorionic gonadotropin, a finding most often reported in osteosarcoma. We present the case of a young woman who presented with a low-level human chorionic gonadotropin level which, after resection of her recurrent giant cell tumor of bone with secondary aneurysmal bone cyst-like change, became undetectable in her blood. Furthermore, cells within the aneurysmal bone cyst component were immunohistochemically positive for β-human chorionic gonadotropin. This is the first report of such a finding in the literature.

  4. Low-frequency hearing preceded the evolution of giant body size and filter feeding in baleen whales.

    PubMed

    Park, Travis; Evans, Alistair R; Gallagher, Stephen J; Fitzgerald, Erich M G

    2017-02-08

    Living baleen whales (mysticetes) produce and hear the lowest-frequency (infrasonic) sounds among mammals. There is currently debate over whether the ancestor of crown cetaceans (Neoceti) was able to detect low frequencies. However, the lack of information on the most archaic fossil mysticetes has prevented us from determining the earliest evolution of their extreme acoustic biology. Here, we report the first anatomical analyses and frequency range estimation of the inner ear in Oligocene (34-23 Ma) fossils of archaic toothed mysticetes from Australia and the USA. The cochlear anatomy of these small fossil mysticetes resembles basilosaurid archaeocetes, but is also similar to that of today's baleen whales, indicating that even the earliest mysticetes detected low-frequency sounds, and lacked ultrasonic hearing and echolocation. This suggests that, in contrast to recent research, the plesiomorphic hearing condition for Neoceti was low frequency, which was retained by toothed mysticetes, and the high-frequency hearing of odontocetes is derived. Therefore, the low-frequency hearing of baleen whales has remained relatively unchanged over the last approximately 34 Myr, being present before the evolution of other signature mysticete traits, including filter feeding, baleen and giant body size.

  5. Rapidly growing giant cell tumor of bone in a skeletally immature girl.

    PubMed

    Akaike, Gensuke; Ueno, Teruko; Matsumoto, Seiichi; Motoi, Noriko; Matsueda, Kiyoshi

    2016-04-01

    Giant cell tumor of bone (GCTB) in skeletally immature patients is rare, and little is known regarding how fast GCTB can grow. We report a case of a 10-year-old skeletally immature girl with pathologically proven GCTB with obvious growth plate invasion that showed surprisingly rapid growth over only 14 days. A radiograph of the left knee revealed well-circumscribed, geographic bone destruction at the distal metaphysis of the femur with a focal cortical defect, suggesting a pathologic fracture. No abnormal mineralization or periosteal reaction was seen. A CT without contrast and an MRI demonstrated a homogeneous lesion with cortical disruption posteriorly and laterally with a slight soft tissue extension. Biopsy showed numerous multinucleated giant cells and spindle-shaped mononuclear cells without any sign of malignancy, suggesting GCTB. However, rapid lesion enlargement and destruction of the surrounding cortex were noted 14 days after biopsy. Considering the amount of bone destruction, traditional treatment of curettage and bone cement would not suffice to sustain structural strength. In addition, considering the patient's age, the tumor location, and the aggressive course, a malignant tumor, especially a giant cell-rich osteosarcoma, could not be excluded. Therefore, en bloc resection, including the growth plate and prosthetic replacement, were performed. Confirmation of GCTB was made from a pathologic evaluation, and a breach to the growth plate was identified. Since very little inflammatory reaction, degenerative change, or aneurysmal, bone, cyst-like change was found, the growth plate invasion was confirmed as due to GCTB extension, not due to the preoperative biopsy.

  6. Fluctuations of the transcription factor ATML1 generate the pattern of giant cells in the Arabidopsis sepal

    PubMed Central

    Meyer, Heather M; Teles, José; Formosa-Jordan, Pau; Refahi, Yassin; San-Bento, Rita; Ingram, Gwyneth; Jönsson, Henrik; Locke, James C W; Roeder, Adrienne H K

    2017-01-01

    Multicellular development produces patterns of specialized cell types. Yet, it is often unclear how individual cells within a field of identical cells initiate the patterning process. Using live imaging, quantitative image analyses and modeling, we show that during Arabidopsis thaliana sepal development, fluctuations in the concentration of the transcription factor ATML1 pattern a field of identical epidermal cells to differentiate into giant cells interspersed between smaller cells. We find that ATML1 is expressed in all epidermal cells. However, its level fluctuates in each of these cells. If ATML1 levels surpass a threshold during the G2 phase of the cell cycle, the cell will likely enter a state of endoreduplication and become giant. Otherwise, the cell divides. Our results demonstrate a fluctuation-driven patterning mechanism for how cell fate decisions can be initiated through a random yet tightly regulated process. DOI: http://dx.doi.org/10.7554/eLife.19131.001 PMID:28145865

  7. Immunohistochemical detection of the receptor activator of nuclear factor Kappa B ligand and c-fos in giant cell granuloma.

    PubMed

    Ahmed, Atif A; Dunlap, Charles

    2016-01-01

    Giant cell granuloma (GCG) is an intraosseous giant cell fibroblastic lesion that predominantly affects the jaw bones in children and adults. Despite its frequent local progression and destructive effect, it is traditionally considered reparative or reactive in nature. The receptor activator of nuclear factor Kappa B ligand (RANKL), a member of the tumor necrosis factor family and the transcription factor c-fos play a major role in osteoclast proliferation and differentiation. In this study, we examined the expression of RANKL and c-fos in lesional tissues from seven patients with GCG. Automated immunohistochemical staining was performed on formalin-fixed paraffin-embedded sections from 7 cases, using antibodies against RANKL, c-fos and p53. All tissues showed nuclear staining for c-fos and cytoplasmic staining for RANKL. The staining was strong, diffuse and observed in both mononuclear lesional cells and giant cells. No staining was observed with p53. Expression of RANKL and c-fos in this lesion, similar to what has been reported in giant cell tumors of bone, suggests a similar pathogenesis and hence a potential response to anti-RANKL inhibitors. A larger study is needed to confirm these findings and define the relationship of this lesion to other giant cell-rich bone lesions.

  8. N-BODY SIMULATIONS OF SATELLITE FORMATION AROUND GIANT PLANETS: ORIGIN OF ORBITAL CONFIGURATION OF THE GALILEAN MOONS

    SciTech Connect

    Ogihara, Masahiro; Ida, Shigeru E-mail: ida@geo.titech.ac.jp

    2012-07-01

    As the number of discovered extrasolar planets has been increasing, diversity of planetary systems requires studies of new formation scenarios. It is important to study satellite formation in circumplanetary disks, which is often viewed as analogous to formation of rocky planets in protoplanetary disks. We investigated satellite formation from satellitesimals around giant planets through N-body simulations that include gravitational interactions with a circumplanetary gas disk. Our main aim is to reproduce the observable properties of the Galilean satellites around Jupiter through numerical simulations, as previous N-body simulations have not explained the origin of the resonant configuration. We performed accretion simulations based on the work of Sasaki et al., in which an inner cavity is added to the model of Canup and Ward. We found that several satellites are formed and captured in mutual mean motion resonances outside the disk inner edge and are stable after rapid disk gas dissipation, which explains the characteristics of the Galilean satellites. In addition, owing to the existence of the disk edge, a radial compositional gradient of the Galilean satellites can also be reproduced. An additional objective of this study is to discuss orbital properties of formed satellites for a wide range of conditions by considering large uncertainties in model parameters. Through numerical experiments and semianalytical arguments, we determined that if the inner edge of a disk is introduced, a Galilean-like configuration in which several satellites are captured into a 2:1 resonance outside the disk inner cavity is almost universal. In fact, such a configuration is produced even for a massive disk {approx}> 10{sup 4} g cm{sup -2} and rapid type I migration. This result implies the inevitability of a Galilean satellite formation in addition to providing theoretical predictions for extrasolar satellites. That is, we can predict a substantial number of exomoon systems in the 2

  9. Processus and recessus adhaerentes: giant adherens cell junction systems connect and attract human mesenchymal stem cells.

    PubMed

    Wuchter, Patrick; Boda-Heggemann, Judit; Straub, Beate K; Grund, Christine; Kuhn, Caecilia; Krause, Ulf; Seckinger, Anja; Peitsch, Wiebke K; Spring, Herbert; Ho, Anthony D; Franke, Werner W

    2007-06-01

    Substrate-adherent cultured cells derived from human bone marrow or umbilical cord blood ("mesenchymal stem cells") are of special interest for regenerative medicine. We report that such cells, which can display considerable heterogeneity with respect to their cytoskeletal protein complement, are often interconnected by special tentacle-like cell processes contacting one or several other cells. These processus adhaerentes, studded with many (usually small) puncta adhaerentia and varying greatly in length (up to more than 400 microm long), either contact each other in the intercellular space ("ET touches") or insert in a tight-fitting manner into deep plasma membrane invaginations (recessus adhaerentes), thus forming a novel kind of long (up to 50 microm) continuous cuff-like junction (manubria adhaerentia). The cell processes contain an actin microfilament core that is stabilized with ezrin, alpha-actinin, and myosin and accompanied by microtubules, and their adhering junctions are characterized by a molecular complement comprising the transmembrane glycoproteins N-cadherin and cadherin-11, in combination with the cytoplasmic plaque proteins alpha- and beta-catenin, together with p120(ctn), plakoglobin, and afadin. The processes are also highly dynamic and rapidly foreshorten as cell colonies approach a denser state of cell packing. These structures are obviously able to establish cell-cell connections, even over long distances, and can form deep-rooted and tight cell-cell adhesions. The possible relationship to similar cell processes in the embryonic primary mesenchyme and their potential in cell sorting and tissue formation processes in the body are discussed.

  10. Delayed reaction after an octopus bite showing a giant cell-rich granulomatous dermatitis/panniculitis.

    PubMed

    Misago, Noriyuki; Inoue, Takuya; Narisawa, Yutaka

    2008-11-01

    Adequate clinical data and a sufficient workup, in addition to the histopathological findings, are frequently required to make a correct diagnosis of granulomatous dermatitis/panniculitis. These lesions with an unexpected etiology may include delayed hypersensitivity granulomatous reactions to various factors, such as metals or marine animal injuries. A 50-year-old male presented with multiple subcutaneous nodules on his right forearm 1 month following an octopus bite at his right wrist. After the disappearance of these lesions, which responded well to low-dose oral prednisone, another type of skin lesion characterized by small, numerous papules reappeared on his right forearm. Histopathologically, a specimen from a subcutaneous nodule showed mostly lobular granulomatous panniculitis, which showed an extensive diffuse infiltrate composed of numerous multinucleated giant cells and epithelioid cells intermingling with lymphocytes and eosinophils. A specimen from a papule that subsequently developed disclosed a diffuse granulomatous dermatitis composed of similar cells and also showed granuloma annulare-like features. This case is considered to be a delayed reaction after an octopus bite showing an unusual giant cell-rich granulomatous dermatitis/panniculitis. Octopus bites should therefore be included among the marine animal injuries, which cause a delayed-type reaction with granulomatous dermatitis/panniculitis.

  11. Immunohistochemical expression of alpha-smooth muscle actin and glucocorticoid and calcitonin receptors in central giant-cell lesions.

    PubMed

    Maiz, Nancy Noya; de la Rosa-García, Estela; Camacho, María Esther Irigoyen

    2016-04-01

    Central giant-cell lesions (CGCLs) are reactive lesions that consist histologically of spindle-shaped stromal cells, (fibroblasts and myofibroblasts) loosely arranged in a fibrous stroma, multinucleated giant cells and mononuclear cells with haemorrhagic areas. This study identified the immunoexpression of alpha-smooth muscle actin in spindle-shaped stromal cells, and glucocorticoid and calcitonin receptors in multinucleated giant cells and mononuclear cells. Their association with the clinical and radiographic characteristics of these lesions was identified. Thirty-five cases of CGCLs were studied. Expression of alpha-smooth muscle actin, glucocorticoid and calcitonin was evaluated by immunohistochemistry. The labelling index was 100 times the quotient of the number of positive cells divided by the total number of cells of each type. Logistic regression analysis was applied. Alpha-smooth muscle actin was positive (54%) for spindle stromal cells (myofibroblasts). A significant association was observed with root resorption (P = 0.004) and cortical bone destruction (P = 0.024). Glucocorticoid immunoexpression was positive for 99% of the giant cells and 86.7% of the mononuclear cells. Glucocorticoid immunoexpression in the mononuclear cells was associated with root resorption (P = 0.031). A longer evolution time was associated with lower immunoexpression of glucocorticoid (OR 12.4: P = 0.047). Calcitonin immunoexpression was positive in 86% of the giant cells. Immunoexpression of calcitonin was associated with age (P = 0.040). Myofibroblasts are important components of CGCLs, stromal cells and alpha-smooth muscle. Actin immunoexpression was associated with root and cortical bone resorption. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. [Value of clusterin expression in pathologic diagnosis and histogenesis of giant cell tumor of tendon sheath].

    PubMed

    Tang, Li; Zhou, Jun; Jiang, Zhi-ming; Zhang, Hui-zhen; Liu, Liang; Chen, Jie

    2012-03-01

    Analyze the immunophenotype of the different cells in the various subtypes of giant cell tumor of tendon sheath (GCTS) and investigate the value of clusterin in pathological diagnosis and histogenesis of giant cell tumor of tendon sheath. A total of 104 cases of GCTS from the surgical pathology files of Shanghai Jiaotong university affiliated the sixth people's hospital were identified. Immunohistochemistry (IHC) for clusterin, desmin, CD163, CD68, p63, p53, Ki-67 and CD35 was performed on all cases, using EnVision technique. All cases of GCTS were researched, including 44 cases of localized type (L-GCTS), 32 cases of diffused type (D-GCTS), 26 cases of pigmented villonodular synovitis (PVNS) and 2 cases of malignant type. There was a slight female predominance in all these subtypes, and the male to female ratio was about 38:66. L-GCTS usually occured within the small joints (90.9%, 40/44), while D-GCTS, PVNS and M-GCTS commonly occured within the large weight-bearing joints [68.8% (22/32), 100% (26/26) and 2/2 respectively]. Of 74 cases with follow-up, the recurrence rates of L-GCTS, D-GCTS, PVNS and M-GCTS respectively were 30.3% (10/33), 30.4% (7/23), 18.8% (3/16) and 2/2. The different subtypes of GCTS had the same cell components, including the large synovial-like mononuclear cells, the small histiocytoid cells, foamy histiocytes cells, inflammatory cells, fibroblasts and the osteoclast-like multinucleated giant cells. There were obvious differences among immunophenotype of the various cell components in GCTS: the large synovial-like mononuclear cells were strong positive for clusterin, partly positive for desmin and Ki-67, and negative for CD163. The small histiocytoid cells were strong positive for CD163 but negative for clusterin and desmin. The osteoclast-like multinucleated giant cells were strong positive for CD68 but negative for clusterin, CD163 and desmin. Normal synoviocytes were strong positive for clusterin, partly positive for desmin. The number

  13. Correlations between histopathological findings and clinical manifestations in biopsy-proven giant cell arteritis.

    PubMed

    Muratore, Francesco; Boiardi, Luigi; Cavazza, Alberto; Aldigeri, Raffaella; Pipitone, Nicolò; Restuccia, Giovanna; Bellafiore, Salvatore; Cimino, Luca; Salvarani, Carlo

    2016-05-01

    To correlate histopathological features of positive temporal artery biopsy (TAB) and clinical manifestations of the disease in a large single-center population-based cohort of patients with biopsy-proven giant cell arteritis (GCA). A pathologist with expertise in vasculitis and blinded to clinical data and final diagnosis reviewed all TABs performed for suspected GCA at our hospital between January 1986 and December 2013. Histopathologic features evaluated were: the severity of inflammation and intimal hyperplasia, both graded on a semiquantitative scale (mild = 1, moderate = 2, severe = 3), the presence of intraluminal acute thrombosis, calcifications, giant cells, fibrinoid necrosis and laminar necrosis. 274 patients had a final diagnosis of biopsy-proven GCA and were included in the study. Cranial ischemic events (CIEs) were observed in 161 (58.8%), visual manifestations in 79 (28.8%) and permanent (partial or complete) visual loss in 51 (18.6%) patients. Predictors for the development of CIEs were older age (OR = 1.057, 95% CI 1.019-1.097, p = 0.003), lower ESR values (OR = 0.990, 95% CI 0.981-0.999, p = 0.026) as well as the presence of giant cells (OR = 1.848, 95% CI 1.045-3.269, p = 0.035) and laminar necrosis at TAB (OR = 2.334, 95% CI 1.187-4.587, p = 0.014). Predictors for the development of permanent visual loss were lower CRP values (OR = 0.906, 95% CI 0.827-0.992, p = 0.033) and the presence of calcifications at TAB (OR = 3.672, 95% CI 1.479-9.121, p = 0.005). Fibrinoid necrosis was not observed in any of the TABs evaluated. Pathological features of TAB may predict some manifestations of GCA. These findings may have implications for patients' management. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Evaluation for clinical predictors of positive temporal artery biopsy in giant cell arteritis.

    PubMed

    Rieck, Kevin L; Kermani, Tanaz A; Thomsen, Kristine M; Harmsen, William S; Karban, Matthew J; Warrington, Kenneth J

    2011-01-01

    To examine the clinical predictors of a positive temporal artery biopsy (TAB) among patients suspected of having giant cell arteritis. We conducted a retrospective study of all consecutive patients who underwent TAB by a single surgeon (K.L.R.) at the Department of Oral Maxillofacial Surgery from April 30, 2002, to June 29, 2006. The medical records were reviewed for the clinical symptoms, laboratory findings, biopsy results, and final diagnosis. The variables of interest as predictors of positive biopsy findings were analyzed using logistic regression analysis. During the study period, 82 patients underwent TAB. Histologic evidence of arteritis was present in 22 patients (26.8%). Two (2.4%) were diagnosed with giant cell arteritis clinically but had negative TAB findings. The patients presenting with weight loss or jaw claudication were more likely to have a positive TAB finding (odds ratio 4.50, 95% confidence interval 1.45 to 13.93; and odds ratio 3.71, 95% confidence interval 1.28 to 10.76, respectively). No laboratory findings were predictive of a positive TAB finding. Prednisone use before TAB also was not associated with a decreased likelihood of a positive finding. Patients suspected of having giant cell arteritis were more likely to have a positive TAB finding if they presented with weight loss or jaw claudication. In the present series, corticosteroid therapy before biopsy did not affect the rate of positive TAB findings. Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  15. Insular and Sylvian Fissure Dermoid Cyst with Giant Cell Reactivity: Case Report and Review of Literature.

    PubMed

    Garces, Juanita; Mathkour, Mansour; Beard, Bryce; Sulaiman, Olawale A R; Ware, Marcus L

    2016-09-01

    Dermoid cysts are rare intracranial tumors that are most commonly found infratentorially and along the midline. Characterized by slow growth and often found incidentally, these lesions can nonetheless have severe complications, notably rupture leading to chemical meningitis. They infrequently present as a supratentorial and lateralized mass. As such, sylvian fissure dermoid cysts are exquisitely rare. We present a rare case of a dermoid cyst with giant cell reactivity suggestive of focal rupture and chronic inflammation. A 61-year-old female presented with new-onset seizures. Magnetic resonance imaging revealed a right insular mass measuring 4.3 × 4.5 cm with compression of the ipsilateral frontal and temporal lobes. The mass was nonenhancing; however, it was bright on diffusion-weighted imaging, suggesting a dermoid cyst. She underwent craniotomy for tumor resection. Histologic analysis revealed keratinizing squamous epithelium, sebaceous glands, and hair follicles associated with giant cell reaction involving the capsule of the cyst consisted with dermoid cyst. At 2.5 years post operation, she is seizure free and without evidence of recurrence. The dermoid cyst in our patient was not grossly ruptured, but histopathologic analysis revealed giant cell reactivity, which may indicate focal rupture or chronic inflammation. The relationship between rupture of dermoid cysts and inflammation is not well elucidated. It is not known whether symptoms occur immediately after rupture or as an acute manifestation of a chronic process following rupture. As these lesions are quite rare and rupture is even rarer, more diligence on our part regarding details of histopathology for dermoid cysts is necessary. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Giant cell arteritis in a 12-year-old girl presenting with nephrotic syndrome.

    PubMed

    El-Sayed, Zeinab A; El-Awady, Hanaa M; Hassan, Zeinab E; Adham, Tamer M H; Mostafa, Hossam M; Elhefnawy, Nadia G

    2014-01-01

    Giant cell arteritis (GCA) is rare in children. The kidneys are generally spared. We present a case of GCA in a 12-year-old girl with severe headache and tender scalp especially over the right temporal area. The right superficial temporal artery was cord like and nodular and the pulsations were barely felt. Several small tender nodular swellings were felt in the occipital area. She had been previously diagnosed as a case of nephrotic syndrome due to underlying membranoproliferative glomerulonephritis. This report is aimed at drawing attention to this rare form of vasculitis in children aiming at decreasing its morbidities.

  17. Varicella Zoster Virus in Temporal Arteries of Patients With Giant Cell Arteritis.

    PubMed

    Gilden, Don; Nagel, Maria

    2015-07-15

    Giant cell arteritis (GCA) is an immune-mediated disease of unknown etiology. Varicella zoster virus (VZV) antigen was found in all of 4 GCA-positive temporal arteries (TAs) but was not present in any of 13 normal TAs. All 4 GCA-positive TAs contained viral antigen in skip areas, mostly in the adventitia and media and least in the intima. Despite formalin fixation, VZV DNA was detected in 2 of 4 GCA-positive, VZV antigen-positive TAs. Skeletal muscle was attached to 3 of 4 TAs, and VZV antigen was found in 2 and VZV DNA in 1. VZV may cause GCA.

  18. Golden bullet-denosumab: early rapid response of metastatic giant cell tumor of the bone.

    PubMed

    Demirsoy, Ugur; Karadogan, Meriban; Selek, Özgür; Anik, Yonca; Aksu, Görkem; Müezzinoglu, Bahar; Corapcioglu, Funda

    2014-03-01

    Giant cell tumor of the bone (GCTB) is usually a benign, locally aggressive tumor with metastatic potential. Histogenesis of GCTB is unknown and a correlation has not been found between histologic and clinical course. For this reason, many authors consider its prognosis unpredictable. Lung metastasis after GCTB treatment is well known and generally has unfavorable outcome, despite varied chemotherapy regimens. Denosumab, which inhibits RANK-RANKL interaction, is a new, promising actor among targeted therapeutic agents for GCTB. In this report, we emphasize on early rapid response to denosumab in metastatic GCTB.

  19. Radiology of giant cell tumors of bone: computed tomography, arthro-tomography, and scintigraphy.

    PubMed

    Hudson, T M; Schiebler, M; Springfield, D S; Enneking, W F; Hawkins, I F; Spanier, S S

    1984-01-01

    Radiologic studies of 50 giant cell tumors of bone in 48 patients were useful in assessing the anatomic extent for planning surgical treatment. Contrast-enhanced computed tomography (CT) provided the most useful and complete evaluation, including soft tissue extent and relationship to major vessels. Angiography was useful when the extraosseous extent and vascular relationships were not entirely clear on CT. Arthro-tomography was the best way to evaluate tumor invasion through subchondral cortex and articular cartilage. Reactive soft tissues, with edema and hyperemia, were difficult to distinguish from tumor tissue on CT and angiograms. Bone scintigrams often showed intense uptake beyond the true tumor limits.

  20. Giant Anterior Chest Wall Basal Cell Carcinoma: An Approach to Palliative Reconstruction

    PubMed Central

    Prendergast, Christina; Leis, Amber

    2016-01-01

    Anterior chest wall giant basal cell carcinoma (GBCC) is a rare skin malignancy that requires a multidisciplinary treatment approach. This case report demonstrates the challenges of anterior chest wall GBCC reconstruction for the purpose of palliative therapy in a 72-year-old female. Surgical resection of the lesion included the manubrium and upper four ribs. The defect was closed with bilateral pectoral advancement flaps, FlexHD, and pedicled VRAM. The palliative nature of this case made hybrid reconstruction more appropriate than rigid sternal reconstruction. In advanced metastatic cancers, the ultimate goals should be to avoid risk for infection and provide adequate coverage for the defect. PMID:28083152

  1. Giant cell arteritis and polymyalgia rheumatica as first manifestation of typical pulmonary carcinoid tumor.

    PubMed

    Aguiar, T; Vincent, M B

    2015-12-23

    Giant cell arteritis (GCA), a systemic vasculitis of unknown origin, may appear rarely as a paraneoplastic syndrome. Cases secondary to pulmonary neuroendocrine tumors have not been reported. A 75-year-old female developed prednisone-responsive GCA/polymyalgia rheumatica (PMR) shortly followed by syndrome of inappropriate antidiuretic hormone secretion. An 8 mm carcinoid lung tumor with positron emission tomography normal uptake was found. After a thoracoscopic tumor resection the patient experienced complete clinical and laboratory remission. This is the first report of GCA with PMR in the context of carcinoid lung tumor. It emphasizes the role of paraneoplastic vasculitis as a possible cause of GCA.

  2. Acute monocular visual loss in carcinomatous hypertrophic pachymeningitis mimicking giant cell arteritis.

    PubMed

    Chan, Jane W

    2006-05-01

    This report describes a 69-year-old woman who presented with acute monocular visual loss, ipsilateral headache, and elevated sedimentation rate (ESR) and C-reactive protein (CRP). Both temporal artery biopsies were negative. Neuroimaging, dural biopsy, and breast biopsy all confirmed the diagnosis of carcinomatous hypertrophic pachymeningitis associated with metastatic breast carcinoma. After treatment with corticosteroids, her vision improved. Her clinical presentation initially mimicked the symptoms and signs of giant cell arteritis. Acute monocular visual loss without other cranial nerve palsies may be an uncommon presentation of hypertrophic pachymeningitis from metastatic breast carcinoma.

  3. Acute monocular visual loss in carcinomatous hypertrophic pachymeningitis mimicking giant cell arteritis.

    PubMed

    Chan, Jane W

    2006-02-01

    This report describes a 69-year-old woman who presented with acute monocular visual loss, ipsilateral headache, and elevated sedimentation rate and C-reactive protein. Both temporal artery biopsies were negative. Neuroimaging, dural biopsy, and breast biopsy all confirmed the diagnosis of carcinomatous hypertrophic pachymeningitis associated with metastatic breast carcinoma. After treatment with corticosteroids, her vision improved. Her clinical presentation initially mimicked the symptoms and signs of giant cell arteritis. Acute monocular visual loss without other cranial nerve palsies may be an uncommon presentation of hypertrophic pachymeningitis from metastatic breast carcinoma.

  4. Giant cell arteritis: the internist should not be a lone rider in this potentially blinding condition.

    PubMed

    Bidgoli, S; Cordonnier, M

    2013-01-01

    We report the case of a 66-year-old woman with visual loss due to anterior ischaemic optic neuropathy. The diagnosis of giant cell arteritis was made on the basis of classic clinical characteristics and haematological abnormalities. Despite corticosteroid treatment, involvement of the other eye occured, resulting in a bilateral and permanent loss of vision. The follow-up was marked by two relapses within the 6 months after the first episode. In order to prevent blindness, ophthalmologists should be familiar with this disorder and should actively participate in the treatment, not leaving the internist deciding alone about tapering corticotherapy.

  5. The plant cell inhibitor KRP6 is involved in multinucleation and cytokinesis disruption in giant-feeding cells induced by root-knot nematodes.

    PubMed

    Vieira, Paulo; de Almeida Engler, Janice

    2015-01-01

    The plant cell cycle inhibitor gene KRP6 has been investigated in roots infected by plant-parasitic root-knot nematodes (Meloidogyne spp.). Unexpectedly, KRP6 overexpressing lines revealed a distinct role for this specific KRP as an activator of the mitotic cell cycle. This function was confirmed in Arabidopsis thaliana suspension cultures ectopically expressing KRP6. A blockage in the mitotic exit was observed in cell suspensions and in giant cells resulted in the appearance of multi-nucleated cells. KRP6 expression during nematode infection and the similarity in phenotypes among KRP6 overexpressing cell cultures and giant-cell morphology strongly suggest that KRP6 is involved in multinucleation and acytokinesis occurring in giant-cells. Once again nematodes have been shown to manipulate the plant cell cycle machinery in order to promote gall establishment.

  6. Pleomorphic giant cell carcinoma of the urinary bladder: an extreme form of tumour de-differentiation.

    PubMed

    Samaratunga, Hemamali; Delahunt, Brett; Egevad, Lars; Adamson, Michael; Hussey, David; Malone, Greg; Hoyle, Kirsten; Nathan, Tim; Kerle, David; Ferguson, Peter; Nacey, John N

    2016-03-01

    Vesical pleomorphic giant cell carcinoma (PGCC) is a variant of urothelial carcinoma (UC) characterized by highly pleomorphic tumour with giant cells. Fewer than 10 cases have been reported, and our aim was to determine the clinical and pathological features of a series of tumours from a specialized uropathology laboratory. Thirteen cases of PGCC of the bladder were identified. There were nine males and four females, ranging in age from 53 to 92 years (mean 72 years). Associated conventional high-grade UC was seen in eight cases, while three cases also had micropapillary UC and one plasmacytoid UC. UC in situ (CIS) was present in five cases and occasional bizarre cells were seen in both UC and CIS. The proportion of PGCC present varied from 40% to 100% of tumour. Immunostaining performed on 10 cases showed uniform positivity for CK 8/18 and AE1/AE3, while most tumours were positive for CK7, CK20, uroplakin III and GATA binding protein 3 (GATA3). β-human chorionic gonadotrophin (β-hCG) was negative. Of 10 patients with follow-up, five died within 1 year and four are alive with tumour. The association of PGCC with UC and an overlap in immunoexpression suggests that PGCC represents an extreme form of UC de-differentiation. © 2015 John Wiley & Sons Ltd.

  7. Internal triggering of volcanic eruptions: tracking overpressure regimes for giant magma bodies

    NASA Astrophysics Data System (ADS)

    Tramontano, Samantha; Gualda, Guilherme A. R.; Ghiorso, Mark S.

    2017-08-01

    Understanding silicic eruption triggers is paramount for deciphering explosive volcanism and its potential societal hazards. Here, we use phase equilibria modeling to determine the potential role of internal triggering - wherein magmas naturally evolve to a state in which eruption is inevitable - in rhyolitic magma bodies. Whole-rock compositions from five large to super-sized rhyolitic deposits are modeled using rhyolite-MELTS. By running simulations with varying water contents, we can track crystallization and bubble exsolution during magma solidification. We use simulations with variable enthalpy and fixed pressure for the five compositions. The interplay between bubble exsolution and crystallization can lead to an increase in the system volume, which can lead to magma overpressurization. We find that internal triggering is possible for high-silica rhyolite magmas crystallizing at pressures below 300 MPa (<11 km depth in the crust), revealing a window of eruptibility within the upper crust from which high-silica eruptions emanate. At higher pressures, the critical overpressure threshold for eruption is only reached once crystallinities are high, >50 wt.%, which makes magma immobile - high-silica rhyolite eruptions from such depths would require external triggering, but examples are scarce or entirely absent. Calculated crystallinities at which the critical overpressure threshold is reached compare favorably with observed crystal contents in natural samples for many systems, suggesting that internal evolution plays a critical role in triggering eruptions. Systems in which fluid saturation happens late relative to crystallization or in which degassing is effective can delay or avoid internal triggering. We argue that priming by crystallization and bubble exsolution is critical for magma eruption, and external triggering serves simply as the final blow - rather than being the driving force - of explosive rhyolitic eruptions.

  8. PET/CT in giant cell arteritis: High (18)F-FDG uptake in the temporal, occipital and vertebral arteries.

    PubMed

    Rehak, Z; Vasina, J; Ptacek, J; Kazda, T; Fojtik, Z; Nemec, P

    (18)F-FDG PET/CT imaging is useful in patients with fever of unknown origin and can detect giant cell arteritis in extracranial large arteries. However, it is usually assumed that temporal arteries cannot be visualized with a PET/CT scanner due to their small diameter. Three patients with clinical symptoms of temporal arteritis were examined using a standard whole body PET/CT protocol (skull base - mid thighs) followed by a head PET/CT scan using the brain protocol. High (18)F-FDG uptake in the aorta and some arterial branches were detected in all 3 patients with the whole body protocol. Using the brain protocol, head imaging led to detection of high (18)F-FDG uptake in temporal arteries as well as in their branches (3 patients), in occipital arteries (2 patients) and also in vertebral arteries (3 patients). Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  9. Widespread headache as the first clinical manifestation of giant cell arteritis in patients affected by polymyalgia rheumatica.

    PubMed

    Manzo, Ciro

    2016-01-01

    In giant cell arteritis (GCA) headache of new onset due to inflammatory involvement of the temporal artery (TA) represents a diagnostic criterion. A widespread headache (WH) with scalp tenderness due to cranial arteritis can represent another manifestation of GCA. In 225 elderly patients with polymyalgia rheumatica (PMR) followed in our rheumatologic outpatient clinic from 2004 until June 2016, the frequency of WH as the first clinical manifestation of GCA was evaluated. Among 26 patients with GCA+PMR (11.6% of total), 5 (23.07%) had WH as first clinical manifestation of GCA without TA. In all these patients TA colour duplex sonography (CDS) and 18-fluorodeoxyglucose positron emission tomography (FDG-PET) with total body contrast-enhanced CT was consistent with the diagnosis of arteritis. TA biopsy was not performed. High doses of prednisone (1 mg/kg/day) led to the immediate and total disappearance of the headache. The widespread headache should be considered as the first symptom GCA and in cases of suspicion of vasculitis patients should have a full diagnostics examination. Colour duplex sonography and FDG-PET with total body contrast-enhanced CT are useful tools for non-invasive diagnosis of GCA.

  10. Widespread headache as the first clinical manifestation of giant cell arteritis in patients affected by polymyalgia rheumatica

    PubMed Central

    2016-01-01

    Introduction In giant cell arteritis (GCA) headache of new onset due to inflammatory involvement of the temporal artery (TA) represents a diagnostic criterion. A widespread headache (WH) with scalp tenderness due to cranial arteritis can represent another manifestation of GCA. Material and methods In 225 elderly patients with polymyalgia rheumatica (PMR) followed in our rheumatologic outpatient clinic from 2004 until June 2016, the frequency of WH as the first clinical manifestation of GCA was evaluated. Results Among 26 patients with GCA+PMR (11.6% of total), 5 (23.07%) had WH as first clinical manifestation of GCA without TA. In all these patients TA colour duplex sonography (CDS) and 18-fluorodeoxyglucose positron emission tomography (FDG-PET) with total body contrast-enhanced CT was consistent with the diagnosis of arteritis. TA biopsy was not performed. High doses of prednisone (1 mg/kg/day) led to the immediate and total disappearance of the headache. Conclusions The widespread headache should be considered as the first symptom GCA and in cases of suspicion of vasculitis patients should have a full diagnostics examination. Colour duplex sonography and FDG-PET with total body contrast-enhanced CT are useful tools for non-invasive diagnosis of GCA. PMID:27994267

  11. Peptidergic modulation of the membrane potential of the Schwann cell of the squid giant nerve fibre.

    PubMed Central

    Evans, P D; Reale, V; Villegas, J

    1986-01-01

    The effects of a range of neuropeptides were investigated on the membrane potential of the Schwann cells of the giant nerve fibre of the tropical squid. Vasoactive intestinal peptide (VIP) produced a dose-dependent, long-lasting hyperpolarization of the Schwann-cell membrane potential. Among peptides structurally related to VIP, similar effects were produced by peptide histidine isoleucine (PHI) but not by secretin and glucagon. Substance P and somatostatin also hyperpolarized the Schwann-cell membrane potential but via receptor systems distinct from those activated by VIP. Methionine enkephalin ([Met]-enkephalin) blocked the actions of all the above peptides as well as the effects of DL-octopamine and carbachol. The actions of [Met]-enkephalin upon the VIP responses were antagonized by naloxone. VIP produces its effects on the Schwann-cell membrane potential via a receptor system that is independent from those described previously which mediate the effects of carbachol and DL-octopamine. However, VIP can potentiate the effects of the latter systems. The actions of VIP on the Schwann cell are unlikely to be mediated via changes in adenosine 3',5'-cyclic monophosphate (cyclic AMP) levels and are insensitive to changes in the level of extracellular calcium in the superfusate. The actions of VIP are, however, potentiated in the presence of low concentrations of lithium ions suggesting that the VIP receptor may mediate its effects by inducing the hydrolysis of polyphosphatidylinositols in the Schwann-cell membrane. Evidence is presented for the existence of an endogenous VIP-like component in the normal hyperpolarizing action of giant-axon activity on the membrane potential of the Schwann cell. PMID:2435897

  12. Therapeutic Antibodies Targeting CSF1 Impede Macrophage Recruitment in a Xenograft Model of Tenosynovial Giant Cell Tumor

    PubMed Central

    Cheng, Hongwei; Clarkson, Paul W.; Gao, Dongxia; Pacheco, Marina; Wang, Yuzhuo; Nielsen, Torsten O.

    2010-01-01

    Tenosynovial giant cell tumor is a neoplastic disease of joints that can cause severe morbidity. Recurrences are common following local therapy, and no effective medical therapy currently exists. Recent work has demonstrated that all cases overexpress macrophage colony-stimulating factor (CSF1), usually as a consequence of an activating gene translocation, resulting in an influx of macrophages that form the bulk of the tumor. New anti-CSF1 drugs have been developed; however there are no preclinical models suitable for evaluation of drug benefits in this disease. In this paper, we describe a novel renal subcapsular xenograft model of tenosynovial giant cell tumor. Using this model, we demonstrate that an anti-CSF1 monoclonal antibody significantly inhibits host macrophage infiltration into this tumor. The results from this model support clinical trials of equivalent humanized agents and anti-CSF1R small molecule drugs in cases of tenosynovial giant cell tumor refractory to conventional local therapy. PMID:20981142

  13. Therapeutic Antibodies Targeting CSF1 Impede Macrophage Recruitment in a Xenograft Model of Tenosynovial Giant Cell Tumor.

    PubMed

    Cheng, Hongwei; Clarkson, Paul W; Gao, Dongxia; Pacheco, Marina; Wang, Yuzhuo; Nielsen, Torsten O

    2010-01-01

    Tenosynovial giant cell tumor is a neoplastic disease of joints that can cause severe morbidity. Recurrences are common following local therapy, and no effective medical therapy currently exists. Recent work has demonstrated that all cases overexpress macrophage colony-stimulating factor (CSF1), usually as a consequence of an activating gene translocation, resulting in an influx of macrophages that form the bulk of the tumor. New anti-CSF1 drugs have been developed; however there are no preclinical models suitable for evaluation of drug benefits in this disease. In this paper, we describe a novel renal subcapsular xenograft model of tenosynovial giant cell tumor. Using this model, we demonstrate that an anti-CSF1 monoclonal antibody significantly inhibits host macrophage infiltration into this tumor. The results from this model support clinical trials of equivalent humanized agents and anti-CSF1R small molecule drugs in cases of tenosynovial giant cell tumor refractory to conventional local therapy.

  14. Binucleate trophoblast giant cells in the water buffalo (Bubalus bubalis) placenta.

    PubMed

    Carvalho, A F; Klisch, K; Miglino, M A; Pereira, F T V; Bevilacqua, E

    2006-01-01

    The binucleate trophoblast giant cells (BNC) of the water buffalo, Bubalus bubalis, placenta were studied, with emphasis on the synthesis of BNC-specific proteins. Placentomal tissues of 27 water buffalos (2-10 months of pregnancy) were processed for light and electron microscopy. The frequency of BNCs was 20% of the trophoblastic cells in 2-3-month placentas and increased to 27% in the later stages. Ultrastructurally, binucleate cells displayed a prominent granular endoplasmic reticulum and Golgi apparatus, typical of cells involved with protein synthesis and exportation. The buffalo BNCs contained periodic acid-Schiff (PAS)-positive granules and reacted with antisera against bovine placental lactogen, prolactin-related protein-I, and pregnancy-associated glycoproteins. Lectin histochemistry with Dolichos biflorus agglutinin, Vicia villosa agglutinin, and Phaseolus vulgaris leucoagglutinin showed specific staining of BNCs. Different stages of BNC migration and fusion with uterine epithelial cells were observed. Trinucleate feto-maternal hybrid cells were the typical outcome of cell fusions. These cells underwent degeneration, with typical morphological features of apoptosis. The results revealed a strong homology between water buffalo and cattle BNCs concerning cell morphology, protein expression, glycosylation pattern, and characteristics of cell migration and fusion.

  15. CTCFL (BORIS) mRNA Expression in a Peripheral Giant Cell Granuloma of the Oral Cavity

    PubMed Central

    Zambrano-Galván, Graciela; Reyes-Romero, Miguel; Bologna-Molina, Ronell; Almeda-Ojeda, Oscar Eduardo; Lemus-Rojero, Obed

    2014-01-01

    Peripheral giant cell granuloma (PGCG) is a relatively common benign reactive lesion of the oral cavity which can occur at any age. CTCFL/BORIS (CTCF like/Brother of the Regulator of Imprinted Sites) and CTCF (CCCTC-binding factor) are paralogous genes with an important role in the regulation of gene expression, genomic imprinting, and nuclear chromatin insulators regulation. BORIS expression promotes cell immortalization and growth while CTCF has tumor suppressor activity; the expression pattern may reflect the reverse transcription silencing of BORIS. The aim of this work was to describe a histopathological and molecular approach of an 8-year-old pediatric male patient with PGCG diagnosis. It was observed that the PGCG under study expressed CTCF as well as BORIS mRNAs alongside with the housekeeping gene GAPDH, which may be related to possible genetic and epigenetic changes in normal cells of oral cavity. PMID:25114808

  16. Oncocytic Pleomorphic Adenoma of Palatal Salivary Gland with Macrophages and Giant Cells Associated with Cholesterol Crystals

    PubMed Central

    Sarode, Gargi S.; Sarode, Sachin C.; Patil, Shankargouda; Anil, Sukumaran

    2016-01-01

    Pleomorphic adenoma (PA) is the most common salivary gland tumor characterized by histo-morphological diversity in the form of myxoid, hyalinized, chondroid, osseous, and squamous areas. In this paper, we report a rare case of predominantly oncocytic variant of PA in a 45-year-old male patient on the posterior palatal region. Microscopic examination showed homogenous eosinophilic cellular mass composed of epithelial components arranged in the form of tubular and solid patterns. The polygonal and oval cells showed abundant dark eosinophilic granular cytoplasm. The cell borders were distinct with a central nucleus showing prominent nucleoli. Interestingly at few places, cholesterol clefts were seen surrounded by macrophages and giant cells. The tumor was surgically excised with no evidence of recurrence after 2 years. PMID:28028431

  17. Basic Fibroblast Growth Factor Stimulates the Proliferation of Bone Marrow Mesenchymal Stem Cells in Giant Panda (Ailuropoda melanoleuca).

    PubMed

    Wang, Jun-Jie; Liu, Yu-Liang; Sun, Yuan-Chao; Ge, Wei; Wang, Yong-Yong; Dyce, Paul W; Hou, Rong; Shen, Wei

    2015-01-01

    It has been widely known that the giant panda (Ailuropoda melanoleuca) is one of the most endangered species in the world. An optimized platform for maintaining the proliferation of giant panda mesenchymal stem cells (MSCs) is very necessary for current giant panda protection strategies. Basic fibroblast growth factor (bFGF), a member of the FGF family, is widely considered as a growth factor and differentiation inducer within the stem cell research field. However, the role of bFGF on promoting the proliferation of MSCs derived from giant panda bone marrow (BM) has not been reported. In this study, we aimed to investigate the role of bFGF on the proliferation of BM-MSCs derived from giant panda. MSCs were cultured for cell proliferation analysis at 24, 48 and 72 hrs following the addition of bFGF. With increasing concentrations of bFGF, cell numbers gradually increased. This was further demonstrated by performing 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) cell proliferation assay, 5-Bromo-2-deoxyUridine (BrdU) labeling and cell cycle testing. Furthermore, the percentage of MSCs that were OCT4 positive increased slightly following treatment with 5 ng/ml bFGF. Moreover, we demonstrated that the extracellular signal-regulated kinase (ERK) signaling pathway may play an important role in the proliferation of panda MSCs stimulated by bFGF. In conclusion, this study suggests that giant panda BM-MSCs have a high proliferative capacity with the addition of 5 ng/ml bFGF in vitro.

  18. Basic Fibroblast Growth Factor Stimulates the Proliferation of Bone Marrow Mesenchymal Stem Cells in Giant Panda (Ailuropoda melanoleuca)

    PubMed Central

    Wang, Jun-Jie; Liu, Yu-Liang; Sun, Yuan-Chao; Ge, Wei; Wang, Yong-Yong; Dyce, Paul W.; Hou, Rong; Shen, Wei

    2015-01-01

    It has been widely known that the giant panda (Ailuropoda melanoleuca) is one of the most endangered species in the world. An optimized platform for maintaining the proliferation of giant panda mesenchymal stem cells (MSCs) is very necessary for current giant panda protection strategies. Basic fibroblast growth factor (bFGF), a member of the FGF family, is widely considered as a growth factor and differentiation inducer within the stem cell research field. However, the role of bFGF on promoting the proliferation of MSCs derived from giant panda bone marrow (BM) has not been reported. In this study, we aimed to investigate the role of bFGF on the proliferation of BM-MSCs derived from giant panda. MSCs were cultured for cell proliferation analysis at 24, 48 and 72 hrs following the addition of bFGF. With increasing concentrations of bFGF, cell numbers gradually increased. This was further demonstrated by performing 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) cell proliferation assay, 5-Bromo-2-deoxyUridine (BrdU) labeling and cell cycle testing. Furthermore, the percentage of MSCs that were OCT4 positive increased slightly following treatment with 5 ng/ml bFGF. Moreover, we demonstrated that the extracellular signal-regulated kinase (ERK) signaling pathway may play an important role in the proliferation of panda MSCs stimulated by bFGF. In conclusion, this study suggests that giant panda BM-MSCs have a high proliferative capacity with the addition of 5 ng/ml bFGF in vitro. PMID:26375397

  19. Giant Cell Tumor of the Tendon Sheath With Discordant Metabolism as a False Positive on Staging of Mantle Cell Lymphoma.

    PubMed

    Rezaee, Alireza; Chen, Wengen; Dilsizian, Vasken; Chen, Qing; Kimball, Amy S

    2015-10-01

    A baseline F-FDG PET/CT scan in a patient with mantle cell lymphoma showed diffuse minimally FDG-avid lymphadenopathy and splenomegaly. There was also a focus of uptake in the left subscapularis muscle without a CT correlate. A post-chemotherapy scan showed interval decrease in size, and resolution of FDG uptake, of the lymph nodes and spleen. Persistent activity was seen in the subscapularis muscle. Posttreatment biopsy of the FDG-avid lesion showed a benign giant cell tumor of tendon sheath. This case illustrates that a lesion with a markedly discordant SUV should raise suspicion for a second process.

  20. Giant cell arteritis: laboratory predictors of a positive temporal artery biopsy.

    PubMed

    Walvick, Matthew D; Walvick, Michael P

    2011-06-01

    To identify laboratory predictors of a positive temporal artery biopsy. Cross-sectional study using retrospective electronic data base review. There were 3001 patients who had a temporal artery biopsy. The electronic database of a large health maintenance organization was searched for all patients who had a temporal artery biopsy performed from 1997 to 2006. Odds ratios for erythrocyte sedimentation rate, C-reactive protein (CRP), and platelet count values associated with a positive temporal artery biopsy. Four hundred fifty-nine cases of biopsy-proven giant cell arteritis were identified. The odds of a positive biopsy were 1.5 times greater with an erythrocyte sedimentation rate of 47 to 107 mm/hr, 5.3 times greater with a CRP >2.45 mg/dL, and 4.2 times greater with platelets >400,000/μL. In this largest population-based giant cell arteritis study in the United States to date, we reaffirm Hayreh's finding of the significance of a CRP level >2.45 mg/dL in predicting a positive biopsy. Our findings support the literature suggesting that CRP and thrombocytosis may be stronger predictors of positive biopsy than erythrocyte sedimentation rate. The authors have no proprietary or commercial interest in any of the materials discussed in this article. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  1. Denosumab treatment of inoperable or locally advanced giant cell tumor of bone

    PubMed Central

    Borkowska, Aneta; Goryń, Tomasz; Pieńkowski, Andrzej; Wągrodzki, Michał; Jagiełło-Wieczorek, Ewelina; Rogala, Paweł; Szacht, Milena; Rutkowski, Piotr

    2016-01-01

    Giant cell tumor of bone (GCTB) is an osteolytic, locally aggressive tumor that rarely metastasizes and typically occurs in the bones. At present, the primary treatment for GCTB is curettage with local adjuvants. Giant cells express receptor activator of nuclear factor-κB ligand (RANKL). Denosumab, a RANKL inhibitor appears to present an effective therapeutic option in advanced cases of GCTB. The aim of the present study was to confirm the efficacy of denosumab in large group of patients with locally advanced GCTB. A total of 35 patients with histologically confirmed GCTB that were treated with denosumab with no participation in clinical trials between May 2013 and September 2015 were included in the present study. Denosumab treatment was administered until complete tumor resection was feasible or tumor progression or unacceptable toxicity had occurred. The mean denosumab treatment duration was 7.4 months. A total of 17 patients received surgery following denosumab treatment: 11 patients underwent wide en bloc resection with prosthesis implantation in 10 cases and 6 patients were treated with intralesional curettage. Tumor progression was observed in 2 patients that underwent intralesional curettage without prosthesis implantation. In addition, tumor progression was observed during denosumab treatment in 2 patients that had previously undergone radiotherapy. The overall 1-year progression-free survival rate was 92.8%. Thus, for patients with advanced, unresectable, progressive or symptomatic pretreated GCTB, denosumab provides a therapeutic option not previously available, which has become the standard therapy in multidisciplinary management of GCTB. PMID:28101196

  2. Denosumab treatment of inoperable or locally advanced giant cell tumor of bone.

    PubMed

    Borkowska, Aneta; Goryń, Tomasz; Pieńkowski, Andrzej; Wągrodzki, Michał; Jagiełło-Wieczorek, Ewelina; Rogala, Paweł; Szacht, Milena; Rutkowski, Piotr

    2016-12-01

    Giant cell tumor of bone (GCTB) is an osteolytic, locally aggressive tumor that rarely metastasizes and typically occurs in the bones. At present, the primary treatment for GCTB is curettage with local adjuvants. Giant cells express receptor activator of nuclear factor-κB ligand (RANKL). Denosumab, a RANKL inhibitor appears to present an effective therapeutic option in advanced cases of GCTB. The aim of the present study was to confirm the efficacy of denosumab in large group of patients with locally advanced GCTB. A total of 35 patients with histologically confirmed GCTB that were treated with denosumab with no participation in clinical trials between May 2013 and September 2015 were included in the present study. Denosumab treatment was administered until complete tumor resection was feasible or tumor progression or unacceptable toxicity had occurred. The mean denosumab treatment duration was 7.4 months. A total of 17 patients received surgery following denosumab treatment: 11 patients underwent wide en bloc resection with prosthesis implantation in 10 cases and 6 patients were treated with intralesional curettage. Tumor progression was observed in 2 patients that underwent intralesional curettage without prosthesis implantation. In addition, tumor progression was observed during denosumab treatment in 2 patients that had previously undergone radiotherapy. The overall 1-year progression-free survival rate was 92.8%. Thus, for patients with advanced, unresectable, progressive or symptomatic pretreated GCTB, denosumab provides a therapeutic option not previously available, which has become the standard therapy in multidisciplinary management of GCTB.

  3. Head and neck giant cell arteritis: an autoimmune disease with many faces.

    PubMed

    Wirth, Markus; Schirmer, Lucas; Hofauer, Benedikt; Lenschow, Magdalena; Loos, Daria; Thuermel, Klaus; Knopf, Andreas

    2017-09-01

    A high rate of infrequent presentations of giant cell arteritis were seen in the ENT department and should be anticipated as a differential diagnosis in every older patient with odynophagia with high CRP values without cause in thorough ENT examination. To describe the clinical manifestation of head and neck giant cell arteritis and to derive a diagnostic pathway covering atypical cases. Single-center, retrospective analysis of cases with GCA in the head and neck region (HN-GCA) (2002-2012) to describe the clinical presentation and to derive a diagnostic pathway covering manifestations presenting to an ENT department. Sixty-five patients were newly diagnosed with HN-GCA in the department of otolaryngology, ophthalmology and neurology. The most frequent symptoms were loss of vision (83%) and new onset headache (63%). Eight patients (12%) presented with infrequent manifestations, predominantly in the department of otorhinolaryngology. The most common atypical presentation (50%) was odynophagia in conjunction with high CRP values misleading to an infectious cause and delaying diagnosis. A diagnostic pathway for GCA was derived based on the ACR classification criteria and the clinical findings.

  4. Subependymal giant cell astrocytomas in patients with tuberous sclerosis complex: considerations for surgical or pharmacotherapeutic intervention.

    PubMed

    Wheless, James W; Klimo, Paul

    2014-11-01

    Tuberous sclerosis complex is a genetic disorder caused by mutations in either the TSC1 or TSC2 gene that can result in the growth of hamartomas in multiple organ systems. Subependymal giant cell astrocytomas are slow-growing brain tumors associated primarily with tuberous sclerosis complex. They are usually located in the ventricles, often near the foramen of Monro, where they can cause an obstruction if they grow too large, leading to increased intracranial pressure. Surgery to remove a tumor has been the mainstay of treatment but can be associated with postoperative morbidity and mortality. Not all tumors and/or patients are suitable for surgery. The recent development of mammalian target of rapamycin inhibitors that target the pathway affected by TSC1/TSC2 mutations offers a novel pharmacotherapeutic option for these patients. We review the timing and use of surgery versus pharmacotherapy for the treatment of subependymal giant cell astrocytoma in patients with tuberous sclerosis complex. © The Author(s) 2013.

  5. Review of isolated ascending aortitis: differential diagnosis, including syphilitic, Takayasu's and giant cell aortitis.

    PubMed

    Tavora, Fabio; Burke, Allen

    2006-08-01

    The image of tree-barking and proximal aortic root dilatation is firmly entrenched in the minds of practising pathologists as representing syphilis until proven otherwise. We discuss the differential diagnosis of syphilitic aortitis, Takayasu's disease, and giant cell aortitis, with a review of the literature and brief overview of other types of aortitis. As a starting point, we report a case of non-specific, or idiopathic, aortitis with aneurysm that was initially misdiagnosed as syphilitic aortitis. We then review the literature and emphasise the lack of histological data and histopathological criteria for the diagnosis of non-infectious aortitis and the implications for treatment in cases of isolated aortitis. Tree-barking is a non-specific finding in aortitis of any aetiology, and syphilitic aortitis in developed countries is rare. It is still unclear if there are histological features that separate Takayasu's disease and giant cell arteritis. In the majority of patients presenting with aortic root aneurysms, aortitis is an isolated finding not associated with autoimmune disease. Despite a plethora of literature, a histological classification of aortitis has yet to be attempted.

  6. Endopolyploidy in irradiated p53-deficient tumour cell lines: Persistence of cell division activity in giant cells expressing Aurora B- kinase

    PubMed Central

    Erenpreisa, Jekaterina; Ivanov, Andrei; Wheatley, Sally P; Kosmacek, Elizabeth A; Ianzini, Fiorenza; Anisimov, Alim P; Mackey, Michael; Davis, Paul J; Plakhins, Grigorijs; Illidge, Timothy M

    2008-01-01

    Recent findings including computerized live imaging suggest that polyploidy cells transiently emerging after severe genotoxic stress (and named ‘endopolyploid cells’) may have a role in tumour regrowth after anti-cancer treatment. Until now, mostly the factors enabling metaphase were studied in them. Here we investigate the mitotic activities and the role of Aurora B, in view of potential de-polyploidisation of these cells, because Aurora B- kinase is responsible for coordination and completion of mitosis. We observed that endopolyploid giant cells are formed in irradiated p53 tumours in several ways: (1) by division/fusion of daughter cells creating early multi-nucleated cells; (2) by asynchronous division/fusion of sub-nuclei of these multinucleated cells; (3) by a series of polyploidising mitoses reverting replicative interphase from aborted metaphase and forming giant cells with a single nucleus; (4) by micronucleation of arrested metaphases enclosing genome fragments; or (5) by incomplete division in the multipolar mitoses forming late multi-nucleated giant cells. We also observed that these activities are able to release para-diploid cells, although they do so infrequently. Although after a substantial delay, apoptosis typically occurs in these cells, we also found that roughly 2% of endopolyploid cells evade apoptosis and senescence arrest and continue mitotic activities. In this article we describe that catalytically active aurora B-kinase is expressed in the nuclei of many interphase endopolyploid cells, as well as being present at the centromeres, mitotic spindle and cleavage furrow during their mitotic efforts. The totally micronucleated giant cells (containing subgenomic fragments in multiple micronuclei) represented the only minor fraction, which failed to undergo mitosis and Aurora B was absent from it. These observations suggest that most endopolyploid tumour cells are not reproductively inert and that aurora B may contribute to the establishment

  7. Twist1 in tumor cells and α-smooth muscle actin in stromal cells are possible biomarkers for metastatic giant basal cell carcinoma.

    PubMed

    Motegi, Sei-ichiro; Yamada, Kazuya; Ishikawa, Osamu

    2013-08-01

    We previously reported a case of giant basal cell carcinoma (BCC) in a 75-year-old Japanese man, who subsequently developed a pulmonary metastasis. With regard to the pathogenesis of metastasis of BCC, recently, it has been reported that high levels of expression of Twist1 and N-cadherin in primary and metastatic tumor cells, suggesting that Twist1 expression and an epithelial-mesenchymal transition (EMT) of tumor cells are important for the promotion of tumor invasion and subsequent metastasis. In this report, we identified the expressions of Twist1 in tumor cells and α-smooth muscle actin (α-SMA) in stromal cells in the primary and metastatic sites of giant BCC. These results suggest that Twist1-induced EMT of tumor cells might have been associated with distant organ metastasis in our case, and the presence of α-SMA-positive myofibroblasts surrounding a BCC nest can be one of hallmarks of the aggressiveness of BCC.

  8. Early transcriptomic events in microdissected Arabidopsis nematode-induced giant cells.

    PubMed

    Barcala, Marta; García, Alejandra; Cabrera, Javier; Casson, Stuart; Lindsey, Keith; Favery, Bruno; García-Casado, Gloria; Solano, Roberto; Fenoll, Carmen; Escobar, Carolina

    2010-02-01

    Root-knot nematodes differentiate highly specialized feeding cells in roots (giant cells, GCs), through poorly characterized mechanisms that include extensive transcriptional changes. While global transcriptome analyses have used galls, which are complex root structures that include GCs and surrounding tissues, no global gene expression changes specific to GCs have been described. We report on the differential transcriptome of GCs versus root vascular cells, induced in Arabidopsis by Meloidogyne javanica at a very early stage of their development, 3 days after infection (d.p.i.). Laser microdissection was used to capture GCs and root vascular cells for microarray analysis, which was validated through qPCR and by a promoter-GUS fusion study. Results show that by 3 d.p.i., GCs exhibit major gene repression. Although some genes showed similar regulation in both galls and GCs, the majority had different expression patterns, confirming the molecular distinctiveness of the GCs within the gall. Most of the differentially regulated genes in GCs have no previously assigned function. Comparisons with other transcriptome analyses revealed similarities between GCs and cell suspensions differentiating into xylem cells. This suggests a molecular link between GCs and developing vascular cells, which represent putative GC stem cells. Gene expression in GCs at 3 d.p.i. was also found to be similar to crown galls induced by Agrobacterium tumefaciens, a specialized root biotroph.

  9. Roe Protein Hydrolysates of Giant Grouper (Epinephelus lanceolatus) Inhibit Cell Proliferation of Oral Cancer Cells Involving Apoptosis and Oxidative Stress

    PubMed Central

    Yang, Jing-Iong; Tang, Jen-Yang; Liu, Ya-Sin; Wang, Hui-Ru; Lee, Sheng-Yang; Yen, Ching-Yu

    2016-01-01

    Roe protein hydrolysates were reported to have antioxidant property but the anticancer effects were less addressed, especially for oral cancer. In this study, we firstly used the ultrafiltrated roe hydrolysates (URH) derived from giant grouper (Epinephelus lanceolatus) to evaluate the impact of URH on proliferation against oral cancer cells. We found that URH dose-responsively reduced cell viability of two oral cancer cells (Ca9-22 and CAL 27) in terms of ATP assay. Using flow cytometry, URH-induced apoptosis of Ca9-22 cells was validated by morphological features of apoptosis, sub-G1 accumulation, and annexin V staining in dose-responsive manners. URH also induced oxidative stress in Ca9-22 cells in terms of reactive oxygen species (ROS)/superoxide generations and mitochondrial depolarization. Taken together, these data suggest that URH is a potential natural product for antioral cancer therapy. PMID:27195297

  10. Tsc2 null murine neuroepithelial cells are a model for human tuber giant cells, and show activation of an mTOR pathway.

    PubMed

    Onda, Hiroaki; Crino, Peter B; Zhang, Hongbing; Murphey, Ryan D; Rastelli, Luca; Gould Rothberg, Bonnie E; Kwiatkowski, David J

    2002-12-01

    Cortical tubers are developmental brain malformations in the tuberous sclerosis complex (TSC) that cause epilepsy and autism in TSC patients whose pathogenesis is uncertain. Tsc2 null murine neuroepithelial progenitor (NEP) cells display persistent growth when growth factors are withdrawn, express GFAP at high levels, and have reduced expression of a set of early neuronal lineage markers. Tsc2 null NEP cells exhibit aberrant differentiation into giant cells that express both beta III-tubulin and GFAP and that are morphologically similar to giant cells in human tubers. Tsc2 null giant cells and tuber giant cells have similar transcriptional profiles. Tsc2 null NEP cells express high levels of phosphorylated S6kinase, S6, Stat3, and 4E-BP-1, which is reversed by treatment with rapamycin, an inhibitor of mTOR. We conclude that giant cells in human tubers likely result from a complete loss of TSC2 expression and activation of an mTOR pathway during cortical development.

  11. 'Salvage Treatment' of Aggressive Giant Cell Tumor of Bones with Denosumab

    PubMed Central

    Vaishya, Raju; Vijay, Vipul

    2015-01-01

    Giant cell tumor of the bone (GCTB) presents as a lytic lesion of epiphyseometaphyseal regions of the long bones usually during the second to the fourth decade with female predilection. Histologically, they are formed of neoplastic mononuclear cells with a higher receptor activator of nuclear factor kappa-B ligand (RANKL) expression responsible for the aggressive osteolytic nature of the tumour. RANKL helps in the formation and functioning of osteoclasts. A newer molecule, Denosumab, is a monoclonal antibody directed against RANKL and thus prevents the formation and function of osteoclasts. Management of refractory, multicentric, recurrent, or metastatic GCTB remains challenging as achieving a tumor-free margin surgically is not always possible. Denosumab may play a crucial role, especially in the management of such difficult lesions. We present three cases of locally aggressive GCTB (involving proximal humerus, sacrum, and proximal femur) that were treated and responded very well to Denosumab therapy. PMID:26251767

  12. The giant protein Ebh is a determinant of Staphylococcus aureus cell size and complement resistance.

    PubMed

    Cheng, Alice G; Missiakas, Dominique; Schneewind, Olaf

    2014-03-01

    Staphylococcus aureus USA300, the clonal type associated with epidemic community-acquired methicillin-resistant S. aureus (MRSA) infections, displays the giant protein Ebh on its surface. Mutations that disrupt the ebh reading frame increase the volume of staphylococcal cells and alter the cross wall, a membrane-enclosed peptidoglycan synthesis and assembly compartment. S. aureus ebh variants display increased sensitivity to oxacillin (methicillin) as well as susceptibility to complement-mediated killing. Mutations in ebh are associated with reduced survival of mutant staphylococci in blood and diminished virulence in mice. We propose that Ebh, following its secretion into the cross wall, contributes to the characteristic cell growth and envelope assembly pathways of S. aureus, thereby enabling complement resistance and the pathogenesis of staphylococcal infections.

  13. An Explanation of the Photoinduced Giant Dielectric Constant of Lead Halide Perovskite Solar Cells.

    PubMed

    Almond, Darryl P; Bowen, Chris R

    2015-05-07

    A photoinduced giant dielectric constant of ~10(6) has been found in impedance spectroscopy measurements of lead halide perovskite solar cells. We report similar effects in measurements of a porous lead zirconate titanate (PZT) sample saturated with water. The principal effect of the illumination of the solar cell and of the introduction of water into the pore volume of the PZT sample is a significant increase in conductivity and dielectric loss. This is shown to exhibit low frequency power law dispersion. Application of the Kramers-Kronig relationships show the large measured values of permittivity to be related to the power law changes in conductivity and dielectric loss. The power law dispersions in the electrical responses are consistent with an electrical network model of microstructure. It is concluded that the high apparent values of permittivity are features of the microstructural networks and not fundamental effects in the two perovskite materials.

  14. Giant Host Red Blood Cell Membrane Mimicking Polymersomes Bind Parasite Proteins and Malaria Parasites.

    PubMed

    Najer, Adrian; Thamboo, Sagana; Palivan, Cornelia G; Beck, Hans-Peter; Meier, Wolfgang

    2016-01-01

    Malaria is an infectious disease that needs to be addressed using innovative approaches to counteract spread of drug resistance and to establish or optimize vaccination strategies. With our approach, we aim for a dual action with drug- and 'vaccine-like' activity against malaria. By inhibiting entry of malaria parasites into host red blood cells (RBCs) - using polymer vesicle-based (polymersome) nanomimics of RBC membranes - the life cycle of the parasite is interrupted and the exposed parasites are accessible to the host immune system. Here, we describe how host cell-sized RBC membrane mimics, formed with the same block copolymers as nanomimics, also bind the corresponding malaria parasite ligand and whole malaria parasites, similar to nanomimics. This was demonstrated using fluorescence imaging techniques and confirms the suitability of giant polymersomes (GUVs) as simple mimics for RBC membranes.

  15. The Giant Protein Ebh Is a Determinant of Staphylococcus aureus Cell Size and Complement Resistance

    PubMed Central

    Cheng, Alice G.; Missiakas, Dominique

    2014-01-01

    Staphylococcus aureus USA300, the clonal type associated with epidemic community-acquired methicillin-resistant S. aureus (MRSA) infections, displays the giant protein Ebh on its surface. Mutations that disrupt the ebh reading frame increase the volume of staphylococcal cells and alter the cross wall, a membrane-enclosed peptidoglycan synthesis and assembly compartment. S. aureus ebh variants display increased sensitivity to oxacillin (methicillin) as well as susceptibility to complement-mediated killing. Mutations in ebh are associated with reduced survival of mutant staphylococci in blood and diminished virulence in mice. We propose that Ebh, following its secretion into the cross wall, contributes to the characteristic cell growth and envelope assembly pathways of S. aureus, thereby enabling complement resistance and the pathogenesis of staphylococcal infections. PMID:24363342

  16. Identification of candidate microbial sequences from inflammatory lesion of giant cell arteritis.

    PubMed

    Gordon, Lynn K; Goldman, Melissa; Sandusky, Hallie; Ziv, Nurit; Hoffman, Gary S; Goodglick, Todd; Goodglick, Lee

    2004-06-01

    Giant cell arteritis (GCA) is a granulomatous inflammatory disease of medium and large arteries which is prevalent in the elderly population. The etiology of GCA is unknown, although the immunologic features suggest the possible presence of a microorganism. Our group has examined whether microbial DNA fragments were present at GCA lesions and whether such microbial fragments could be associated with disease pathogenesis. Initial identification of microbial sequences was performed using genomic representational difference analysis (RDA). Laser dissecting microscopy was used to isolate cells from GCA lesions and adjacent uninvolved temporal artery. Using genomic RDA, we isolated 10 gene fragments; three of these sequences had high homology with prokaryotic genes and were considered high-priority candidates for further study. An examination of serum from GCA(+) individuals (in contrast to healthy age-matched controls) showed the presence of IgG which recognized in vitro translated proteins from these clones.

  17. Giant-cell interstitial pneumonia and hard-metal pneumoconiosis. A clinicopathologic study of four cases and review of the literature

    SciTech Connect

    Ohori, N.P.; Sciurba, F.C.; Owens, G.R.; Hodgson, M.J.; Yousem, S.A.

    1989-07-01

    We report four cases of giant-cell interstitial pneumonia that occurred in association with exposure to hard metals. All patients presented with chronic interstitial lung disease and had open-lung biopsies that revealed marked interstitial fibrosis, cellular interstitial infiltrates, and prominent intraalveolar macrophages as well as giant cells displaying cellular cannibalism. We also review the literature to determine the sensitivity and specificity of giant-cell interstitial pneumonia for hard-metal pneumoconiosis. Although hard-metal pneumoconiosis may take the form of usual interstitial pneumonia, desquamative interstitial pneumonia, and giant-cell interstitial pneumonia, the finding of giant-cell interstitial pneumonia is almost pathognomonic of hard-metal disease and should provoke an investigation of occupational exposure. 25 references.

  18. Protein Expression Profiling of Giant Cell Tumors of Bone Treated with Denosumab.

    PubMed

    Mukaihara, Kenta; Suehara, Yoshiyuki; Kohsaka, Shinji; Akaike, Keisuke; Tanabe, Yu; Kubota, Daisuke; Ishii, Midori; Fujimura, Tsutomu; Kazuno, Saiko; Okubo, Taketo; Takagi, Tatsuya; Yao, Takashi; Kaneko, Kazuo; Saito, Tsuyoshi

    2016-01-01

    Giant cell tumors of bone (GCTB) are locally aggressive osteolytic bone tumors. Recently, some clinical trials have shown that denosumab is a novel and effective therapeutic option for aggressive and recurrent GCTB. This study was performed to investigate the molecular mechanism underlying the therapeutic effect of denosumab. Comparative proteomic analyses were performed using GCTB samples which were taken before and after denosumab treatment. Each expression profile was analyzed using the software program to further understand the affected biological network. One of identified proteins was further evaluated by gelatin zymography and an immunohistochemical analysis. We identified 13 consistently upregulated proteins and 19 consistently downregulated proteins in the pre- and post-denosumab samples. Using these profiles, the software program identified molecular interactions between the differentially expressed proteins that were indirectly involved in the RANK/RANKL pathway and in several non-canonical subpathways including the Matrix metalloproteinase pathway. The data analysis also suggested that the identified proteins play a critical functional role in the osteolytic process of GCTB. Among the most downregulated proteins, the activity of MMP-9 was significantly decreased in the denosumab-treated samples, although the residual stromal cells were found to express MMP-9 by an immunohistochemical analysis. The expression level of MMP-9 in the primary GCTB samples was not correlated with any clinicopathological factors, including patient outcomes. Although the replacement of tumors by fibro-osseous tissue or the diminishment of osteoclast-like giant cells have been shown as therapeutic effects of denosumab, the residual tumor after denosumab treatment, which is composed of only stromal cells, might be capable of causing bone destruction; thus the therapeutic application of denosumab would be still necessary for these lesions. We believe that the protein expression

  19. Super giant basal cell carcinoma of the abdominal wall: still possible in the 21st century.

    PubMed

    de Bree, Eelco; Laliotis, Aggelos; Manios, Andreas; Tsiftsis, Dimitris D; Melissas, John

    2010-07-01

    Basal cell carcinoma (BCC) is very common and usually encountered when it is small in size. Giant BCC (i.e. greater than 5 cm in diameter) is quite rare and comprises 0.5 percent of all BCC. Extremely rarely, tumors larger than 20 cm have been reported. Herein, a case with an enormous, vegetating BCC of the abdominal wall, 30 x 20 cm in size, is described. This report demonstrates that such a case can still be observed in the civilized world of the 21st century, which remains profoundly astonishing. A literature survey was performed and revealed only 7 cases with such super giant BCC (i.e. larger than 20 cm in diameter). Generally, this tumor attains these enormous proportions due to neglect on the patient's part, and is usually located at sites covered by clothes. Treatment is mainly surgical and generally curative, resulting also in an improved quality of life. Tumor size of more than 10 cm in diameter is associated with increased risk for metastatic disease, severe morbidity and consequently impaired prognosis.

  20. Lethal (2) giant larvae: an indispensable regulator of cell polarity and cancer development.

    PubMed

    Cao, Fang; Miao, Yi; Xu, Kedong; Liu, Peijun

    2015-01-01

    Cell polarity is one of the most basic properties of all normal cells and is essential for regulating numerous biological processes. Loss of polarity is considered a hallmark for cancer. Multiple polarity proteins are implicated in maintenance of cell polarity. Lethal (2) giant larvae (Lgl) is one of polarity proteins that plays an important role in regulating cell polarity, asymmetric division as well as tumorigenesis. Lgl proteins in different species have similar structures and conserved functions. Lgl acts as an indispensable regulator of cell biological function, including cell polarity and asymmetric division, through interplaying with other polarity proteins, regulating exocytosis, mediating cytoskeleton and being involved in signaling pathways. Furthermore, Lgl plays a role of a tumor suppressor, and the aberrant expression of Hugl, a human homologue of Lgl, contributes to multiple cancers. However, the exact functions of Lgl and the underlying mechanisms remain enigmatic. In this review, we will give an overview of the Lgl functions in cell polarity and cancer development, discuss the potential mechanisms underlying these functions, and raise our conclusion of previous studies and points of view about the future studies.

  1. Comparison of tartrate resistant acid phosphatase in a giant cell bone tumor and a spleen infiltrated with hairy cells.

    PubMed

    Lam, K W; Townsend, D; Garza, A; Li, C Y; Yam, L T

    1990-08-01

    Acid phosphatase (E.C.3.1.3.2) in a giant cell bone tumor and a spleen infiltrated with hairy cells was extracted by citrate buffer and then by 0.3 mol/L NaCl. The cationic acid phosphatase in the crude extract was isolated by CM-cellulose chromatography, and further separated by high pressure liquid chromatography. The majority of the tartrate resistant acid phosphatase in the hairy cell spleen was unabsorbed on CM-cellulose and was insensitive to iron. A much larger portion of the acid phosphatase in the bone tumor, than in the spleen, was cationic and was eluted from the column by 0.8 mol/L NaCl. The cationic acid phosphatase was further separated into consecutive peaks of acid phosphatases with different sensitivity to iron. A major portion of acid phosphatase in the giant cell bone tumor was enhanced by iron, while the amounts of iron-enhanced and iron-insensitive acid phosphatase were about the same in the spleen. The differences of the phosphatases in these two types of pathologic specimens indicate the occurrence of two types of enzymes with different biological significance.

  2. Secondary malignant giant cell tumor of bone due to malignant transformation 40 years after surgery without radiation therapy, presenting as fever of unknown origin: a case report.

    PubMed

    Takesako, Hisataka; Osaka, Eiji; Yoshida, Yukihiro; Sugitani, Masahiko; Tokuhashi, Yasuaki

    2016-03-08

    Malignant transformation of giant cell tumors of bones, that is, secondary malignant giant cell tumor of bone, is rare. The most common symptoms are local pain and swelling. There are no prior reports of giant cell tumor of bone with fever of unknown origin at the onset. Here we present a case of a secondary malignant giant cell tumor of bone due to malignant transformation 40 years after surgery without radiation therapy, presenting as fever of unknown origin. A 75-year-old Asian man presented with a 3-week history of continuous pyrexia and left knee pain and swelling. He had been diagnosed at age 35 years with a giant cell tumor of bone of his left distal femur and underwent bone curettage and avascular fibula grafting at that time. Postoperative radiation therapy was not performed. He remained recurrence-free for 40 years after surgery. At age 75, histopathological findings suggested a secondary malignant giant cell tumor of bone. The tumor specimen expressed tumor necrosis factor-α. Neoplastic fever was suspected, and a naproxen test was conducted. His pyrexia showed immediate resolution. Surgery was performed under a diagnosis of a secondary malignant giant cell tumor of bone with neoplastic fever. His pyrexia and inflammatory activities diminished postoperatively. This is the first reported case, to the best of our knowledge, of the detection of a secondary malignant giant cell tumor of bone based on fever of unknown origin after long-term (40 years) follow-up. After curettage and bone grafting, giant cell tumor of bone may transform to malignancies within a few years or even decades after surgery. Therefore, meticulous follow-up is essential. The fever might be attributable to the tumor releasing inflammatory cytokines. Not only pain and swelling but also continuous pyrexia may suggest the diagnosis of a secondary malignant giant cell tumor of bone.

  3. Giant Cell Tumor of the Larynx Treated by Surgery and Adjuvant Denosumab: Case Report and Review of the Literature.

    PubMed

    Yancoskie, Aaron E; Frank, Douglas K; Fantasia, John E; Savona, Steven; Eiseler, Nicole; Reder, Ilan; Kahn, Leonard B

    2015-12-01

    Giant cell tumor of the larynx (GCTL) is a rare entity; only 34 cases have been reported in the literature. We report a case of GCTL in a 46 year-old male presenting clinical, radiographic, histological and therapeutic features. Previously reported cases are also reviewed.

  4. Giant-Cell Tumor of the Distal Ulna Treated by Wide Resection and Ulnar Support Reconstruction: A Case Report

    PubMed Central

    Minami, Akio; Iwasaki, Norimasa; Nishida, Kinya; Motomiya, Makoto; Yamada, Katsuhisa; Momma, Daisuke

    2010-01-01

    Giant-cell tumor of bone occurred in the distal end of the ulna is extremely uncommon. A 23-year-old male had a giant-cell tumor occurred in the distal end of the ulna. After wide resection of the distal segment of the ulna including giant-cell tumor, ulnar components of the wrist joint were reconstructed with modified Sauvé-Kapandji procedure using the iliac bone graft, preserving the triangular fibrocartilage complex and ulnar collateral ligament in order to maintain ulnar support of the wrist, and the proximal stump of the resected ulna was stabilized by tenodesis using the extensor carpi ulnaris tendon. One year after operation, the patient's wrist was pain-free and had a full range of motion. Postoperative X-rays showed no abnormal findings including recurrence of the giant-cell tumor and ulnar translation of the entire carpus. The stability of the proximal stump of the distal ulna was also maintained. PMID:20592994

  5. [Diffuse tenosynovial giant cell tumor of the cervical spine destroying vertebra C6 - a case report].

    PubMed

    Kinkor, Zdeněk; Svoboda, Tomáš; Grossman, Petr; Bludovský, David; Heidenreich, Filip; Švec, Andrej; Mečiarová, Iveta

    2016-01-01

    Presented is a case of 59-year-old woman with longstanding neck pain who has been promptly operated for spinal cord compression. Imaging studies disclosed ill-defined cervical paravertebral soft tissue mass at the level of vertebra C5/6 abutting left-sided intervertebral joint and destroying neighboring both vertebral arch and processus spinosus. Submitted specimen was interpreted as a possible metastatic skeletal process by clinicians and referring pathologist favored diagnosis of giant cell tumor/osteoclastoma of the bone. Microscopic features were consistent with giant cell lesion where uniform mononuclear mosaic stromal component dominated the unevenly distributed loose clusters of osteoclast-like giant cells frequently imparting appearance of peculiar pseudoalveolar spaces. Additionally, alternating geographic xanthomatous and densely hyalinized/ osteoid-like zones with speckled, coarsely granular haemosiderin pigment completed the variegated structural composition. The tumor infiltrated adjacent striated muscles; either original bone structures and/or extracellular matrix deposits were not identified. Immunohistochemical stains with p63, SATB2, desmin, EMA, clusterin and S100protein turned out to be completely negative. FISH analysis revealed no rearrangement of CSF1 gene. The diagnosis of the diffuse tenosynovial giant cell tumor was rendered.

  6. Acute seronegative hepatitis C manifesting itself as adult giant cell hepatitis--a case report and review of literature.

    PubMed

    Kryczka, Wiesław; Walewska-Zielecka, Bozena; Dutkiewicz, Ewa

    2003-08-01

    Adult giant cell hepatitis (AGCH) is a rare event and only about 100 cases have been reported within the last 20 years. The AGCH has been observed in association with viral infection, drug reactions or autoimmune disorders but in many cases its etiology remains unclear. AGCH manifests clinically as severe form of hepatitis histologically characterized by diffuse giant cell transformation of hepatocytes. We report the case of a 39-yr-old man with acute community-acquired hepatitis without previous pathology of the liver. Laboratory data revealed slight hypergammaglobulinemia and high titer of anti-smooth-muscle antibody with negative serology of hepatotropic viruses and absence of other known causes of hepatitis. Preliminary diagnosis of autoimmune hepatitis was established, additionally confirmed by excellent clinical and biochemical improvement during corticosteroid treatment. A liver biopsy showed the typical findings of panlobular syncytial giant cell hepatitis and positive HCV-RNA both in serum and liver. The above verified the diagnosis of acute type C hepatitis manifested histologically as adult giant cell hepatitis. After three months of treatment we withdrew corticosteroids as spontaneous clearance of HCV occurred and the lack of autoantibodies in serum as well as significant improvement of liver histology was ascertained. Within 30 months of the follow-up we have not observed biochemical and immunological abnormalities and control liver biopsy has shown no signs of hepatitis.

  7. Giant cell interstitial pneumonia in a hard-metal worker. Cytologic, histologic and analytical electron microscopic investigation

    SciTech Connect

    Tabatowski, K.; Roggli, V.L.; Fulkerson, W.J.; Langley, R.L.; Benning, T.; Johnston, W.W.

    1988-03-01

    A case of biopsy-proven giant cell interstitial pneumonia in a patient with occupational exposure to hard-metal dust is reported. Bronchial washings performed several days prior to open-lung biopsy yielded an almost exclusive population of nonpigmented alveolar macrophages and pleomorphic, phagocytic multinucleated giant cells. Microorganisms, viral inclusions in the giant cells, epithelioid histiocytes and well-formed granulomas were not seen. This cytologic picture strongly suggests the presence of giant cell interstitial pneumonia in a patient with restrictive lung disease, particularly when exposure to hard-metal dust is known or suspected. A specific diagnosis early in the course of the disease may facilitate removal of the individual from the workplace and forestall the development of end-stage interstitial fibrosis. Additionally, the working environment may be modified to minimize inhalational exposure. Recognition of this entity by the cytopathologist may direct diagnostic efforts toward accurate histologic evaluation and the identification of particulates by microprobe analysis of either cellular or biopsy material.

  8. The role of cyclic nucleotides in modulation of the membrane potential of the Schwann cell of squid giant nerve fibre.

    PubMed Central

    Evans, P D; Reale, V; Villegas, J

    1985-01-01

    The role of cyclic nucleotides in mediating the effects of nicotine cholinergic receptors has been investigated in Schwann cells of the giant nerve fibre of the squid. Elevation of cyclic AMP levels in this preparation by means of the phosphodiesterase inhibitor, theophylline, by the diterpene adenylate cyclase activator, forskolin, and by cyclic nucleotide analogues mimics the action of activating the nicotinic cholinergic receptors in producing a long-lasting hyperpolarization of the membrane potential of the Schwann cell. Theophylline and forskolin also potentiate the effects of carbachol and of neural stimulation on the Schwann cell. The results suggest that the nicotinic receptor of the squid Schwann cell is likely to mediate its effects via a mechanism that activates adenylate cyclase. The results are discussed in terms of the role of cyclic AMP in the complex multistep interaction between the giant axon of the squid and its surrounding Schwann-cell layer. PMID:2991504

  9. Sarcomatoid carcinoma of the renal pelvis with giant cell tumor-like features: case report with immunohistochemical findings.

    PubMed

    Acikalin, Mustafa Fuat; Kabukcuoglu, Sare; Can, Cavit

    2005-02-01

    Sarcomatoid transitional cell carcinoma is a rare entity, in which a malignant, overtly epithelial component coexists with areas having a sarcoma-like appearance. Histological distinction of sarcomatoid carcinomas from carcinosarcomas is often difficult and immunohistochemistry is a helpful diagnostic adjunct in the correct diagnosis. In the present report, we describe an uncommon case of sarcomatoid transitional cell carcinoma of the renal pelvis, associated with giant cell tumor-like features. Immunoperoxidase staining for cytokeratin was positive in spindle cell component, indicating an epithelial origin. The carcinomatous component showed a diffuse membranous reactivity for E-cadherin, whereas the reactivity was sporadic and weaker in the sarcomatoid component, suggesting that the decrease of E-cadherin expression might be associated with the acquisition of sarcomatous morphology. Osteoclast-like multinucleated giant cells were positive for CD68 and negative for p53 oncoprotein, suggesting that they represent a non-neoplastic component that is reactively induced in the tumor stroma.

  10. Diagnosing Light Chain Amyloidosis on Temporal Artery Biopsies for Suspected Giant Cell Arteritis.

    PubMed

    Ghinai, Rosanna A M; Mahmood, Shameem; Mukonoweshuro, Pinias; Webber, Sally; Wechalekar, Ashutosh D; Moore, Sally E

    2017-03-01

    Although still rarely diagnosed, amyloid light chain (AL) amyloidosis is the most common form of systemic amyloidosis. It is characterized by misfolded monoclonal immunoglobulin light chain fragments that accumulate extracellularly as amyloid fibrils, with consequent organ dysfunction. We report 2 such cases where initial symptoms and signs were identical to and mistaken for those of giant cell arteritis, associated with polymyalgia rheumatica. Neither patient responded to high-dose corticosteroids; instead, their temporal artery biopsies revealed amyloid deposits and other investigations confirmed a diagnosis of systemic AL amyloidosis. Review of the literature reveals similar cases of diagnostic confusion spanning 75 years. We have summarized the findings and learning points from cases reported in the past 30 years and highlight the need for increased awareness and investigation of this underrecognized syndrome.

  11. Multifocal VZV vasculopathy with temporal artery infection mimics giant cell arteritis.

    PubMed

    Nagel, Maria A; Bennett, Jeffrey L; Khmeleva, Nelly; Choe, Alexander; Rempel, April; Boyer, Philip J; Gilden, Don

    2013-05-28

    To address the incidence of varicella-zoster virus (VZV) infection in patients with biopsy-negative giant cell arteritis (GCA), we examined archived biopsy-negative temporal arteries from subjects with clinically suspected GCA for the presence of VZV antigen. Formalin-fixed, paraffin-embedded temporal arteries that were pathologically negative for GCA and normal temporal arteries were analyzed immunohistochemically for VZV and herpes simplex virus-1 (HSV-1) antigen. Five (21%) of 24 temporal arteries from patients who were clinically suspect but biopsy negative for GCA revealed VZV but not HSV-1 by immunohistochemical analysis. Thirteen normal temporal arteries did not contain VZV or HSV-1 antigen. All 5 subjects whose temporal arteries contained VZV antigen presented with clinical and laboratory features of GCA and early visual disturbances. Multifocal VZV vasculopathy can present with the full spectrum of clinical features and laboratory abnormalities characteristically seen in GCA.

  12. The ultrasound compression sign to diagnose temporal giant cell arteritis shows an excellent interobserver agreement.

    PubMed

    Aschwanden, M; Imfeld, S; Staub, D; Baldi, T; Walker, U A; Berger, C T; Hess, C; Daikeler, T

    2015-01-01

    To compare the diagnostic performance between a vascular specialist and a rheumatologist not familiar with vascular ultrasound when applying the compression sign for the diagnosis of temporal arteritis. Sixty consecutive patients with suspicion of giant cell arteritis were examined by both examiners. Compression of the temporal artery on both sides (stem and both branches) was performed to define whether signs of vasculitis, no vasculitis or an indefinite result were present. Each examiner was blinded to the result of the other. In 59/60 patients, the examiners found an identical result. The interobserver agreement (Krippendorf alpha) was 0.92. The new compression sign for the diagnosis of temporal arteritis is a simple and robust sonographic marker with an excellent interobserver agreement.

  13. Multifocal VZV vasculopathy with temporal artery infection mimics giant cell arteritis

    PubMed Central

    Nagel, Maria A.; Bennett, Jeffrey L.; Khmeleva, Nelly; Choe, Alexander; Rempel, April; Boyer, Philip J.

    2013-01-01

    Objective: To address the incidence of varicella-zoster virus (VZV) infection in patients with biopsy-negative giant cell arteritis (GCA), we examined archived biopsy-negative temporal arteries from subjects with clinically suspected GCA for the presence of VZV antigen. Methods: Formalin-fixed, paraffin-embedded temporal arteries that were pathologically negative for GCA and normal temporal arteries were analyzed immunohistochemically for VZV and herpes simplex virus-1 (HSV-1) antigen. Results: Five (21%) of 24 temporal arteries from patients who were clinically suspect but biopsy negative for GCA revealed VZV but not HSV-1 by immunohistochemical analysis. Thirteen normal temporal arteries did not contain VZV or HSV-1 antigen. All 5 subjects whose temporal arteries contained VZV antigen presented with clinical and laboratory features of GCA and early visual disturbances. Conclusion: Multifocal VZV vasculopathy can present with the full spectrum of clinical features and laboratory abnormalities characteristically seen in GCA. PMID:23635966

  14. Critical hypercalcemia following discontinuation of denosumab therapy for metastatic giant cell tumor of bone.

    PubMed

    Gossai, Nathan; Hilgers, Megan V; Polgreen, Lynda E; Greengard, Emily G

    2015-06-01

    We report a 14 year-old female with Giant Cell Tumor of Bone, successfully treated with denosumab, who developed critical hypercalcemia after completion of therapy. Five months after her last denosumab treatment, serum calcium rose to 16.5 mg/dL (normal 8.7-10.8 mg/dL), nearly double her prior level of 8.4 mg/dL while receiving denosumab. She required emergent intervention to treat her hypercalcemia, which was attributed to rebound osteoclast activity and osteopetrotic bone. Denosumab is widely used in adults and increasingly in pediatric oncology populations and our experience demonstrates the need for close monitoring for electrolyte derangements following discontinuation.

  15. Current status and unanswered questions on the use of Denosumab in giant cell tumor of bone.

    PubMed

    Gaston, Czar Louie; Grimer, Robert J; Parry, Michael; Stacchiotti, Silvia; Dei Tos, Angelo Paolo; Gelderblom, Hans; Ferrari, Stefano; Baldi, Giacomo G; Jones, Robin L; Chawla, Sant; Casali, Paolo; LeCesne, Axel; Blay, Jean-Yves; Dijkstra, Sander P D; Thomas, David M; Rutkowski, Piotr

    2016-01-01

    Denosumab is a monoclonal antibody to RANK ligand approved for use in giant cell tumour (GCT) of bone. Due to its efficacy, Denosumab is recommended as the first option in inoperable or metastatic GCT. Denosumab has also been used pre-operatively to downstage tumours with large soft tissue extension to allow for less morbid surgery. The role of Denosumab for conventional limb GCT of bone is yet to be defined. Further studies are required to determine whether local recurrence rates will be decreased with the adjuvant use of Denosumab along with surgery. The long term use and toxicity of this agent is unknown as is the proportion of patients with primary or secondary resistance. It is advised that complicated cases of GCT requiring Denosumab treatment should be referred and followed up at expert centres. Collaborative studies involving further clinical trials and rigorous data collection are strongly recommended to identify the optimum use of this drug.

  16. Laser interstitial thermal therapy for subependymal giant cell astrocytoma: technical case report.

    PubMed

    Dadey, David Y A; Kamath, Ashwin A; Leuthardt, Eric C; Smyth, Matthew D

    2016-10-01

    Subependymal giant cell astrocytoma (SEGA) is a rare tumor occurring almost exclusively in patients with tuberous sclerosis complex. Although open resection remains the standard therapy, complication rates remain high. To minimize morbidity, less invasive approaches, such as endoscope-assisted resection, radiosurgery, and chemotherapy with mTOR pathway inhibitors, are also used to treat these lesions. Laser interstitial thermal therapy (LITT) is a relatively new modality that is increasingly used to treat a variety of intracranial lesions. In this report, the authors describe two pediatric cases of SEGA that were treated with LITT. In both patients the lesion responded well to this treatment modality, with tumor shrinkage observed on follow-up MRI. These cases highlight the potential of LITT to serve as a viable minimally invasive therapeutic approach to the management of SEGAs in the pediatric population.

  17. Giant Cell Fibroma of the Buccal Mucosa with Laser Excision: Report of Unusual Case.

    PubMed

    Bagheri, Fatemeh; Rahmani, Somayyeh; Azimi, Somayyeh; Bigom Taheri, Jamileh

    2015-01-01

    Giant Cell Fibroma (GCF) was described as a new entity of fibrous hyperplastic soft tissue. It seems that stimulus from an unexplained origin can have a role in its etiology. Histopathologically GCF is consisted of multinucleated fibroblasts that have oval shape nuclei within the eosinophilic cytoplasm. Surgical excision is the treatment of choice and recurrence is very rare. Here we report a case of relatively large GCF in a 54-year-old man. Gingiva is the common location of GCF. As in our case, it may be mistaken as irritation fibroma especially if it is on the buccal mucosa, the most common location for fibroma. Correct diagnosis is based on biopsy and clinical examination to see surface texture roughness. To minimize bleeding because of its large size an excisional biopsy with Diod laser was performed under local anesthesia for this patient.

  18. Giant Cell Fibroma of the Buccal Mucosa with Laser Excision: Report of Unusual Case

    PubMed Central

    Bagheri, Fatemeh; Rahmani, Somayyeh; Azimi, Somayyeh; Bigom Taheri, Jamileh

    2015-01-01

    Giant Cell Fibroma (GCF) was described as a new entity of fibrous hyperplastic soft tissue. It seems that stimulus from an unexplained origin can have a role in its etiology. Histopathologically GCF is consisted of multinucleated fibroblasts that have oval shape nuclei within the eosinophilic cytoplasm. Surgical excision is the treatment of choice and recurrence is very rare. Here we report a case of relatively large GCF in a 54-year-old man. Gingiva is the common location of GCF. As in our case, it may be mistaken as irritation fibroma especially if it is on the buccal mucosa, the most common location for fibroma. Correct diagnosis is based on biopsy and clinical examination to see surface texture roughness. To minimize bleeding because of its large size an excisional biopsy with Diod laser was performed under local anesthesia for this patient. PMID:26351504

  19. Differentiating giant cell tumor of bone from patellofemoral syndrome: a case study.

    PubMed

    Bonar, Jason; Carr, Shannon Clutton; De Carvalho, Diana; Wunder, Jay S

    2016-03-01

    Balancing the assessment of musculoskeletal dysfunctions with a high level of suspicion for non-mechanical origins can be a challenge for the clinician examining a sports injury. Without timely diagnosis, non-mechanical complaints could result in surgery or loss of limb. This case describes the discovery of a Giant Cell Tumor of Bone (GCTB) following the re-evaluation of an athlete who had undergone five years of conservative management for patellofemoral pain syndrome (PFPS). Knee injuries account for 32.6% of sports injuries with PFPS being the most common and most likely diagnosis for anterior knee pain. GCTB is a benign aggressive bone tumor with a predilection for the juxta-articular region of the knee, comprising up to 23% of all benign bone tumors, and commonly occurs in the second to fourth decades. This case report illustrates the difficulty in accurately diagnosing healthy athletes, reviews common differentials for knee complaints and explores helpful diagnostic procedures.

  20. Ulnar buttress arthroplasty after enbloc resection of a giant cell tumor of the distal ulna

    PubMed Central

    Naik, Monappa A; Sujir, Premjit; Rao, Sharath K; Tripathy, Sujit K

    2013-01-01

    Enbloc resection with or without ulnar stump stabilization is the recommended treatment for giant cell tumors (GCT) of the distal ulna. A few sporadic reports are available where authors have described various procedures to prevent ulnar stump instability and ulnar translation of carpal bones. We report a GCT of the distal ulna in a 43-year-old male which was resected enbloc. The distal radioulnar joint was reconstructed by fixing an iliac crest graft to the distal end of the radius (ulnar buttress arthroplasty) and the ulnar stump was stabilized with extensor carpi ulnaris tenodesis. After a followup at three years, there was no evidence of tumor recurrence or graft resorption; the patient had a normal range of movement of the wrist joint and the functional outcome was excellent as per the score of Ferracini et al. PMID:23682187

  1. Light chain multiple myeloma presenting with spinal plasmacytoma: Unusual radiological appearance mimicking giant cell tumor.

    PubMed

    Satija, Bhawna; Gupta, Rajat; Kumar, Sanyal; Chandoke, Raj

    2015-01-01

    Plasmacytoma, an initial presentation of multiple myeloma, is extremely rare and an unusual cause of spinal cord compression in a young male. A 35-year-old man presented with complaints of progressive weakness and tingling of bilateral lower limbs, severe backache for 3 months, and bladder and bowel incontinence for 1 week duration. Imaging demonstrated lytic destruction of 10 th and 11 th dorsal vertebrae with large soft tissue component and compression of the spinal cord. Biopsy was performed under computed tomography guidance and the histopathology demonstrated presence of plasmacytoma. Serum electrophoresis and bone marrow examination confirmed the diagnosis of light chain multiple myeloma. Though the magnetic resonance imaging the appearance of spinal plasmacytoma is nonspecific, a minibrain appearance has been considered pathognomonic. This case is reported for the unusual radiological appearance of this entity mimicking giant cell tumor.

  2. GIANT CELL TUMOR IN THE PROXIMAL PHALANX WITH PULMONARY METASTASIS: CASE REPORT AND LITERATURE REVIEW

    PubMed Central

    de Medeiros, Frederico Carvalho; de Medeiros, Fernando Carvalho; de Campos Carvalho Lopes, Izabella; de Medeiros, Guilherme Carvalho; de Medeiros, Eduardo Carvalho

    2015-01-01

    This is a case report on a giant cell tumor (GCT) in the proximal phalanx of the third finger of the left hand, with pulmonary metastasis. The patient presented pain in the finger without any previous history of trauma. Clinical examination, radiographic imaging and magnetic resonance imaging were carried out. A histological evaluation was carried out from an incisional biopsy, taking the hypothesis of GCT. The patient underwent amputation of the finger and the diagnosis was confirmed by means of microscopy on the specimen. The patient was followed up because of the risk of lung metastasis, which was shown by radiographic examination and computed tomography on the chest, and thoracotomy was performed. Since then, there has been an improvement in the symptoms that had been reported preoperatively, and no local recurrence or new metastasis has been found. PMID:27027012

  3. Giant Cell Arteritis: An Atypical Presentation Diagnosed with the Use of MRI Imaging

    PubMed Central

    2016-01-01

    Giant cell arteritis (GCA) is the most common primary systemic vasculitis in western countries in individuals over the age of 50. It is typically characterised by the granulomatous involvement of large and medium sized blood vessels branching of the aorta with particular tendencies for involving the extracranial branches of the carotid artery. Generally the diagnosis is straightforward when characteristic symptoms such as headache, jaw claudication, or other ischemic complications are present. Atypical presentations of GCA without “overt” cranial ischemic manifestations have become increasingly recognised but we report for the first time a case of GCA presenting as mild upper abdominal pain and generalized weakness in the context of hyponatremia as the presenting manifestation of vasculitis that was subsequently diagnosed by MRI scanning. This case adds to the literature and emphasises the importance of MRI in the evaluation of GCA patients without “classic” cranial ischemic symptoms. PMID:27493825

  4. Spinal cord infarction in giant cell arteritis associated with scalp necrosis.

    PubMed

    Mustafa, Khader N; Hadidy, Azmy; Joudeh, Anwar; Obeidat, Fatima Nouri; Abdulfattah, Khalid W

    2015-02-01

    Spinal cord infarction is extremely rare in patients with giant cell arteritis (GCA). There are only four case reports in the literature. We describe a 65-year-old man who presented with sudden paraplegia and back pain of 4-days duration with sensory loss below the umbilicus and bilateral scalp necrosis. Magnetic resonance imaging finding was consistent with dorsal spinal cord infarction. Biopsy of the temporal artery confirmed the diagnosis of GCA. The patient was treated with high dose of corticosteroids, which resulted in healing of the scalp ulcerations in 3 weeks, but the paraplegia was irreversible. To our knowledge, this is the first report of spinal cord infarction and simultaneous occurrence of bilateral scalp necrosis in a histopathologically proven GCA. Although literature about spinal cord involvement in GCA is very limited, cord infarction is associated with high mortality and therapeutic challenges since little is understood regarding the pathogenesis that leads to infarction.

  5. Differentiating giant cell tumor of bone from patellofemoral syndrome: a case study

    PubMed Central

    Bonar, Jason; Carr, Shannon Clutton; De Carvalho, Diana; Wunder, Jay S.

    2016-01-01

    Balancing the assessment of musculoskeletal dysfunctions with a high level of suspicion for non-mechanical origins can be a challenge for the clinician examining a sports injury. Without timely diagnosis, non-mechanical complaints could result in surgery or loss of limb. This case describes the discovery of a Giant Cell Tumor of Bone (GCTB) following the re-evaluation of an athlete who had undergone five years of conservative management for patellofemoral pain syndrome (PFPS). Knee injuries account for 32.6% of sports injuries with PFPS being the most common and most likely diagnosis for anterior knee pain. GCTB is a benign aggressive bone tumor with a predilection for the juxta-articular region of the knee, comprising up to 23% of all benign bone tumors, and commonly occurs in the second to fourth decades. This case report illustrates the difficulty in accurately diagnosing healthy athletes, reviews common differentials for knee complaints and explores helpful diagnostic procedures. PMID:27069267

  6. Development of Mega-Aorta Following Incompletely Treated Giant Cell Arteritis

    PubMed Central

    Eton, Darwin; Shah, Atman P.; Merlo, Aurelie; Dill, Karin; Russo, Mark J.

    2014-01-01

    An 82-year-old male presented with a 9.3 cm ascending aorta and arch aneurysm with additional aneurysms of the innominate, right subclavian, and left common carotid arteries. The patient had a history of temporal arteritis that was only briefly treated in 1989 and a 6 cm ascending aortic aneurysm that was repaired in 1993. Our operative strategy was to construct a temporary parallel cerebrovascular circuit for cerebral protection during the redo-sternotomy and aortic arch reconstruction, with the added benefit of permanently excluding the branch arch vessel aneurysms. Pathological analysis of the aortic specimen at the first operation may have identified giant cell arteritis, prompting medical therapy against further disease progression. PMID:26798733

  7. Aortitis due to giant cell arteritis and psoriatic arthritis: An uncommon association.

    PubMed

    García-Cezón de la Cruz, M Del Pilar; Almodóvar, Raquel; García Pérez, Javier; Dhimes, Patricia Fanny; Zarco, Pedro

    We report the case of a 65-year-old woman with psoriatic arthritis who developed aortitis secondary to giant cell arteritis. She presented with a 2-mounth history of dry cough, fever and fatigue. There was no evidence of tumor or infectious processes. Abdominal computed tomographic and computed tomography coronary angiographic findings were suggestive of aortitis. Histological study of a temporal artery biopsy confirmed temporal arteritis. We also review the available literature on this uncommon condition. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  8. Suppressive effect of iron on concanavalin A-induced multinucleated giant cell formation by human monocytes.

    PubMed

    Tahara, Kiyoshi; Nishiya, Koji; Hisakawa, Naoko; Wang, Honggang; Hashimoto, Kozo

    2003-11-01

    Immune dysfunction in patients with iron overload has been reported. Iron disturbed CD2 expression on T-cells, cell-mediated immunity by Th1 cells and monocyte functions including phagocytosis and natural killer activity. In the present study, we examined the effects of iron and desferrioxamine (DFX, an iron chelator) on generation of multinucleated giant cells (MGC) by human monocytes in vitro. Human monocytes were isolated from venous blood and cultured with concanavalin A (Con A) stimulation with additives, ferric citrate (Fe-citrate) or sodium citrate (Na-citrate) or DFX for 4 days. The cells were fixed and subjected to Wright staining. MGC formation was observed under light microscopy. Con A induced MGC formation in a dose-dependent manner, and reached a plateau after 3 days of incubation. MGC formation was suppressed when Con A-stimulated monocytes were cultured with the co-addition of Fe-citrate but not Na-citrate only in the early phase of culture (less than 24 hours). DFX also suppressed MGC formation in a dose-dependent manner. Using flow cytometry analysis, the co-addition of Fe-citrate significantly suppressed CD18 (beta2 integrin) and CD54 (ICAM-I) but not CD11a (alpha integrin) expression on Con A-stimulated monocytes. Iron supressed the generation of MGC by human monocytes in vitro. These observations suggested that iron might affect MGC generation by down-regulation of adhesion molecule expression on monocytes.

  9. p63 as a prognostic marker for giant cell tumor of bone.

    PubMed

    Yanagisawa, Michiro; Kakizaki, Hiroshi; Okada, Kyoji; Torigoe, Tomoaki; Kusumi, Tomomi

    2013-03-01

    Giant cell tumor of bone (GCT) is sometimes difficult to distinguish from other giant-cell-rich tumors such as chondroblastoma (CHB) and aneurysmal bone cyst (ABC). The usefulness of p63 as a diagnostic marker for GCT is controversial. While there have been no reports about p63 as a prognostic marker for local recurrence, various p63-positive rates in GCT have been reported. The purpose of this study was to investigate retrospectively whether p63 is useful as a diagnostic marker and/or a prognostic marker for local recurrence of GCT. This study included 36 patients diagnosed with either GCT (n = 16), CHB (n = 9), ABC (n = 7), or non-ossifying fibroma (NOF) (n = 4). p63 immunostaining was performed for all specimens. The mean p63-positive rate was compared with the four diseases and between the recurrent and non-recurrent cases of GCT. Although the mean p63-positive rate for GCT (36.3%) was statistically higher than that of all other diseases examined (CHB: 15.2%; ABC: 5.8%; NOF: 3.4%), p63 was not specific for GCT. The mean p63-positive rate for recurrent GCT cases (73.6%) was statistically higher than that for non-recurrent cases (29.1%). In the diagnosis of GCT, p63 is a useful but not a conclusive marker. However, p63 did appear to indicate the biological aggressiveness of GCT. Therefore, p63 may help surgeons to estimate the risk of recurrence after surgery and help them to choose the best treatment for each GCT case.

  10. Giant cell tumor of the bone: aggressive case initially treated with denosumab and intralesional surgery.

    PubMed

    von Borstel, Donald; A Taguibao, Roberto; A Strle, Nicholas; E Burns, Joseph

    2017-04-01

    Giant cell tumor of the bone (GCTB) is a locally aggressive benign tumor, which has historically been treated with wide surgical excision. We report a case of a 29-year-old male with histology-proven GCTB of the distal ulna. The initial imaging study was a contrast-enhanced magnetic resonance imaging (MRI) examination of the left wrist, which was from an outside facility performed before presenting to our institution. On the initial MRI, the lesion had homogenous T2-hyperintense and T1-hypointense signal with expansive remodeling of the osseous contour. A radiographic study performed upon presentation to our institution 1 month later showed progression of the lesion with atypical imaging characteristics. After confirming the diagnosis, denosumab therapy was implemented allowing for reconstitution of bone and intralesional treatment. The patient was treated with five doses of denosumab over the duration of 7 weeks. Therapeutic changes of the GCTB were evaluated by radiography and a post-treatment MRI. This MRI was interpreted as suspicious for worsening disease due to the imaging appearance of intralesional signal heterogeneity, increased perilesional fluid-like signal, and circumferential cortical irregularity. However, on subsequent intralesional curettage and bone autografting 6 weeks later, no giant cells were seen on the specimen. Thus, the appearance on the MRI, rather than representing a manifestation of lesion aggressiveness or a non-responding tumor, conversely represented the imaging appearance of a positive response to denosumab therapy. On follow-up evaluation, 5 months after intralesional treatment, the patient had recurrent disease and is now scheduled for wide-excision with joint prosthesis.

  11. [Repairing bone defect with nano-hydroxyapatite and polyamide 66 composite after giant cell tumor operations].

    PubMed

    Zhang, Shu-liang; Zhou, Yong; Duan, Hong; Min, Li; Zhang, Hui; Shi, Rui; Tu, Chong-qia; Pei, Fu-xing

    2012-05-01

    To evaluate the clinical effectiveness and safety of using granular type nano-hydroxyapatite and polyamide 66 (n-HA/PA66) composite in repairing bone defects caused by giant cell tumors. 48 patients with giant cell tumors, who underwent lesion curettage, inactivation and cavities fill-in with granular type n-HA/PA66 from December 2007 to May 2011, were followed up. Routine blood tests, liver and kidney functions, serum calcium and phosphorus, and immunologic parameters were examined before and after the surgeries. Radiological examinations were carried out 1 week and 1, 3, 6 and 12 months post operations to monitor the bone repairing process. The n-HA/ PA66 in bone issues was detected with hematoxylin-eosin staining. 45 patients completed the follow-up. No significant abnormalities in routine blood tests, serum calcium and phosphorus, and immunologic parameters were found pre- and post-operations. Nor abnormal liver and kidney functional lesions were identified. The radiological examination showed gradual increase in the density of the focal zone after bone implanting operations. The bone density of the implanted areas got close to normal 1 year after operations. The histological examination found that osteoblasts grew into the hole of n-HA/PA66; calcium was deposited on the materials; and large amount of osteocytes inlaid into the composite. The composite was integrated into new bone and surrounding tissues. n-HA/PA66 has good biocompatibility and biological safety. It also has good osteoconduction and osteogenesis activity. The n-HA/PA66 composite is one perfect bone repair material.

  12. Multiple skin cancers in a single patient: Multiple pigmented Bowen's disease, giant basal cell carcinoma, squamous cell carcinoma.

    PubMed

    Saini, Ravi; Sharma, Nidhi; Pandey, Kritika; Puri, K J P S

    2015-01-01

    Basal cell carcinoma (BCC) and squamous cell carcinoma are the most common type of nonmelanoma skin cancers (NMSCs). Bowen's disease (BD), a premalignant condition, has a marginal potential (3-5%) to progress to invasive carcinoma. We report here a rarest of a rare case of multiple pigmented BD with overlying squamous cell cancer along with a giant neglected BCC on the scalp of a 76-year-old man. The occurrence of multiple BD and NMSC in a single patient compelled us to explore the following hypothesis: (1) The multiple precancerous and cancerous lesions can be due to common etiopathogenesis. Chronic ultraviolet exposure, immunosupresssion, human papillomavirus infection, dietary factors, and environmental factors including arsenic exposure were probed in to. (2) There is evolution of precancerous lesions into a different type of cancers in different time frame. (3) The new cancerous lesions are subsequent cancers that developed after neglected untreated primary cancer.

  13. Expressions and clinical significance of factors related to giant cell tumor of bone.

    PubMed

    Li, Chong; Zheng, Xiaojuan; Ghert, Michelle; Li, Hai; Wang, Bin; Feng, Yizhong

    2015-01-01

    Giant cell tumor of bone (GCTB) is a relatively rare tumor of bone, characterized by numerous multinucleated cells, severe osteolysis, and local recurrence. To explore the role of S-phase kinase-interacting protein 2 (Skp2), cyclin-dependent kinase inhibitor p27, and the transcription factor E2F-1 expression in the development of GCTB, and the relationship of expression of these proteins with tumor recurrence. Forty-four patients with GCTB were selected and demographic and clinical data were collected. The levels of Skp2, p27, and E2F-1 protein expression were immunohistochemically assessed in surgical specimens. Skp2, p27, and E2F-1 proteins were detected in the nuclei of mononuclear stromal cells. Positive Skp2 expression was observed in 66% (29/44) of GCTB patient samples, and positive p27 expression was found in 39% (17/44) of samples. Within almost all GCTB patients, there was an inverse correlation between Skp2- and p27-positive tumor cells. Positive expression of E2F-1 was present in 28 of 44 (64%) patients. In addition, expression of skp2 and p27, infiltration of soft tissues, and surgical operation were significantly associated with recurrence in patients with GCTB. The immunohistochemical assessment of Skp2, p27 and E2F-1 may be useful in the diagnosis of GCTB and prediction of its prognosis.

  14. The Macronuclear Genome of Stentor coeruleus Reveals Tiny Introns in a Giant Cell.

    PubMed

    Slabodnick, Mark M; Ruby, J Graham; Reiff, Sarah B; Swart, Estienne C; Gosai, Sager; Prabakaran, Sudhakaran; Witkowska, Ewa; Larue, Graham E; Fisher, Susan; Freeman, Robert M; Gunawardena, Jeremy; Chu, William; Stover, Naomi A; Gregory, Brian D; Nowacki, Mariusz; Derisi, Joseph; Roy, Scott W; Marshall, Wallace F; Sood, Pranidhi

    2017-02-20

    The giant, single-celled organism Stentor coeruleus has a long history as a model system for studying pattern formation and regeneration in single cells. Stentor [1, 2] is a heterotrichous ciliate distantly related to familiar ciliate models, such as Tetrahymena or Paramecium. The primary distinguishing feature of Stentor is its incredible size: a single cell is 1 mm long. Early developmental biologists, including T.H. Morgan [3], were attracted to the system because of its regenerative abilities-if large portions of a cell are surgically removed, the remnant reorganizes into a normal-looking but smaller cell with correct proportionality [2, 3]. These biologists were also drawn to Stentor because it exhibits a rich repertoire of behaviors, including light avoidance, mechanosensitive contraction, food selection, and even the ability to habituate to touch, a simple form of learning usually seen in higher organisms [4]. While early microsurgical approaches demonstrated a startling array of regenerative and morphogenetic processes in this single-celled organism, Stentor was never developed as a molecular model system. We report the sequencing of the Stentor coeruleus macronuclear genome and reveal key features of the genome. First, we find that Stentor uses the standard genetic code, suggesting that ciliate-specific genetic codes arose after Stentor branched from other ciliates. We also discover that ploidy correlates with Stentor's cell size. Finally, in the Stentor genome, we discover the smallest spliceosomal introns reported for any species. The sequenced genome opens the door to molecular analysis of single-cell regeneration in Stentor. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Danger signaling protein HMGB1 induces a distinct form of cell death accompanied by formation of giant mitochondria.

    PubMed

    Gdynia, Georg; Keith, Martina; Kopitz, Jürgen; Bergmann, Marion; Fassl, Anne; Weber, Alexander N R; George, Julie; Kees, Tim; Zentgraf, Hans-Walter; Wiestler, Otmar D; Schirmacher, Peter; Roth, Wilfried

    2010-11-01

    Cells dying by necrosis release the high-mobility group box 1 (HMGB1) protein, which has immunostimulatory effects. However, little is known about the direct actions of extracellular HMGB1 protein on cancer cells. Here, we show that recombinant human HMGB1 (rhHMGB1) exerts strong cytotoxic effects on malignant tumor cells. The rhHMGB1-induced cytotoxicity depends on the presence of mitochondria and leads to fast depletion of mitochondrial DNA, severe damage of the mitochondrial proteome by toxic malondialdehyde adducts, and formation of giant mitochondria. The formation of giant mitochondria is independent of direct nuclear signaling events, because giant mitochondria are also observed in cytoplasts lacking nuclei. Further, the reactive oxygen species scavenger N-acetylcysteine as well as c-Jun NH(2)-terminal kinase blockade inhibited the cytotoxic effect of rhHMGB1. Importantly, glioblastoma cells, but not normal astrocytes, were highly susceptible to rhHMGB1-induced cell death. Systemic treatment with rhHMGB1 results in significant growth inhibition of xenografted tumors in vivo. In summary, rhHMGB1 induces a distinct form of cell death in cancer cells, which differs from the known forms of apoptosis, autophagy, and senescence, possibly representing an important novel mechanism of specialized necrosis. Further, our findings suggest that rhHMGB1 may offer therapeutic applications in treatment of patients with malignant brain tumors.

  16. MicroRNA-106b inhibits osteoclastogenesis and osteolysis by targeting RANKL in giant cell tumor of bone

    PubMed Central

    Wang, Ting; Yin, Huabin; Wang, Jing; Li, Zhenxi; Wei, Haifeng; Liu, Zhi'an; Wu, Zhipeng; Yan, Wangjun; Liu, Tielong; Song, Dianwen; Yang, Xinghai; Huang, Quan; Zhou, Wang; Xiao, Jianru

    2015-01-01

    Giant cell tumor (GCT) of bone consists of three major cell types: giant cells, monocytic cells, and stromal cells. From microarray analysis, we found that miR-106b was down-regulated in GCT clinical samples and further determined by fluorescence in situ hybridization. In addition, the expression of novel potential target of miR-106b, RANKL, was elevated in GCT along with previously determined targets in other tumors such as IL-8, MMP2 and TWIST. In a RANKL 3′UTR luciferase reporter assays, agomiR-106b repressed the luciferase activity and the effect was eliminated when the targeting site in the reporter was mutated, suggesting a direct regulation of miR-106b on RANKL mRNA. Moreover, overexpression of miR-106b in GCTSCs through TALEN-mediated site-specific knockin clearly inhibited osteoclastogenesis and osteolysis. By grafting the GCT onto the chick CAM, we confirmed the inhibitory effect of miR-106b on RANKL expression and giant cell formation. Furthermore, in an OVX mouse model, silencing of miR-106b increased RANKL protein expression and promoted bone resorption, while up-regulation of miR-106b inhibited bone resorption. These results suggest that miR-106b is a novel suppressor of osteolysis by targeting RANKL and some other cytokines, which indicates that miR-106b may be a potential therapeutic target for the treatment of GCT. PMID:26053181

  17. Genetic Analysis of Giant Cell Lesions of the Maxillofacial and Axial/Appendicular Skeletons.

    PubMed

    Peacock, Zachary S; Schwab, Joseph H; Faquin, William C; Hornicek, Francis J; Benita, Yair; Ebb, David H; Kaban, Leonard B

    2017-02-01

    To compare the genetic and protein expression of giant cell lesions (GCLs) of the maxillofacial (MF) and axial/appendicular (AA) skeletons. We hypothesized that when grouped according to biologic behavior and not simply by location, MF and AA GCLs would exhibit common genetic characteristics. This was a prospective and retrospective study of patients with GCLs treated at Massachusetts General Hospital from 1993 to 2008. In a preliminary prospective study, fresh tissue from 6 aggressive tumors each from the MF and AA skeletons (n = 12 tumors) was obtained. RNA was extracted and amplified from giant cells (GCs) and stromal cells first separated by laser capture microdissection. Genes highly expressed by GCs and stroma at both locations were determined using an Affymetrix GeneChip analysis. As confirmation, a tissue microarray (TMA) was created retrospectively from representative tissue of preserved pathologic specimens to assess the protein expression of the commonly expressed genes found in the prospective study. Quantification of immunohistochemical staining of MF and AA lesions was performed using Aperio image analysis to determine whether immunoreactivity was predictive of aggressive or nonaggressive behavior. Five highly ranked genes were found commonly in GCs and stroma at each location: matrix metalloproteinase-9 (MMP-9), cathepsin K (CTSK), T-cell immune regulator-1 (TCIRG1), C-type lectin domain family-11, and zinc finger protein-836. MF (n = 40; 32 aggressive) and AA (n = 48; 28 aggressive) paraffin-embedded tumors were included in the TMA. The proteins CTSK, MMP-9, and TCIRG1 were confirmed to have abundant expression within both MF and AA lesions. Only the staining levels for TCIRG1 within the GCs predicted the clinical behavior of the MF lesions. MMP-9, CTSK, and TCIRG1 are commonly expressed by GCLs of the MF and AA skeletons. This supports the hypothesis that these lesions are similar but at different locations. TCIRG1 has not been previously

  18. The tumoricidal properties of inflammatory tissue macrophages and multinucleate giant cells.

    PubMed Central

    Poste, G.

    1979-01-01

    Peritoneal exudate cells from C3H/HeN mice infected with bacille Calmette Guérin (BCG) and subcutaneous inflammatory macrophages from uninfected mice exhibit spontaneous cytotoxicity for tumor cells in vitro, but their tumoricidal activity can be increased by incubation in vitro with lymphokines released by mitogen- or antigen-stimulated lymphocytes. Inflammatory macrophages from these sites are only susceptible to activation in vitro by lymphokines for a short period (less than 4 days) following their initial emigration from the circulation to the site of inflammation. The expression of tumoricidal activity by activated macrophages is similarly short-lived (less than 4 days). Once the tumoricidal state is lost it cannot be restored by further incubation with lymphokines in vitro. Fusion of macrophages to form multinucleate giant cells (MGCs) accompanies the loss of tumoricidal activity and the onset of resistance to activation by lymphokines, but the fusion process is not responsible for these changes, since unfused macrophages are similarly affected. Activation and acquisition of tumoricidal properties is confined to young macrophages recruited from the circulation during acute inflammation. Older macrophages and MGCs in chronic inflammatory lesions in which recruitment of new macrophages has ceased are nontumoricidal and are refractory to activation by lymphokines in vitro. These findings are discussed in relation to the efficiency of macrophage-mediated destruction of tumors in vivo and the amplification of macrophage antitumor activity by immunotherapeutic agents. Images Figure 3 Figure 1 Figure 2 PMID:382866

  19. Cytotoxic effect and tissue penetration of phenol for adjuvant treatment of giant cell tumours

    PubMed Central

    MITTAG, FALK; LEICHTLE, CARMEN; KIECKBUSCH, INA; WOLBURG, HARTWIG; RUDERT, MAXIMILIAN; KLUBA, TORSTEN; LEICHTLE, ULF

    2013-01-01

    Local adjuvant treatment of giant cell tumours (GCTs) of the bone with phenol has led to a significant reduction in recurrence rates. In the current study, the optimal phenol concentration and duration of intralesional exposure were evaluated. Specimens of GCTs were exposed to various concentrations of phenol solution (6, 60 and 80%) for either 1 or 3 min. Following embedding in glutaraldehyde, the tumour cell layers were examined by transmission electron microscopy. Destroyed cell organelles indicated the penetration depth as a sign of denaturation. Incubation of GCT specimens with 6% phenol solution for 3 min resulted in the most tissue damage and the deepest tissue penetration of ∼200 μm. Incubation with 60 and 80% phenol solution reached a penetration depth of only ∼100 μm. Phenol instillation may be used for the treatment of small scattered cellular debris following intralesional curettage; however, it is not suitable for treatment of remaining solid tumour tissue of GCT. The use of high phenol concentrations has no benefit and increases the risk of local or systemic intoxication. PMID:23760940

  20. Cytotoxic effect and tissue penetration of phenol for adjuvant treatment of giant cell tumours.

    PubMed

    Mittag, Falk; Leichtle, Carmen; Kieckbusch, Ina; Wolburg, Hartwig; Rudert, Maximilian; Kluba, Torsten; Leichtle, Ulf

    2013-05-01

    Local adjuvant treatment of giant cell tumours (GCTs) of the bone with phenol has led to a significant reduction in recurrence rates. In the current study, the optimal phenol concentration and duration of intralesional exposure were evaluated. Specimens of GCTs were exposed to various concentrations of phenol solution (6, 60 and 80%) for either 1 or 3 min. Following embedding in glutaraldehyde, the tumour cell layers were examined by transmission electron microscopy. Destroyed cell organelles indicated the penetration depth as a sign of denaturation. Incubation of GCT specimens with 6% phenol solution for 3 min resulted in the most tissue damage and the deepest tissue penetration of ∼200 μm. Incubation with 60 and 80% phenol solution reached a penetration depth of only ∼100 μm. Phenol instillation may be used for the treatment of small scattered cellular debris following intralesional curettage; however, it is not suitable for treatment of remaining solid tumour tissue of GCT. The use of high phenol concentrations has no benefit and increases the risk of local or systemic intoxication.

  1. Huge undifferentiated carcinoma of the pancreas with osteoclast-like giant cells.

    PubMed

    Jo, Sungho

    2014-03-14

    Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (OGCs) is very rare, less than 1% of all pancreatic malignancies, and shows worse prognosis than that of invasive ductal adenocarcinoma of the pancreas. We present a case of en bloc resection for a huge undifferentiated carcinoma with OGCs that invaded the stomach and transverse mesocolon. A 67-year female was admitted for left upper quadrant pain and computed tomography demonstrated a mass occupying the lesser sac and abutting the stomach and pancreas. There were no distant metastases and the patient underwent subtotal pancreatectomy with splenectomy, total gastrectomy, and segmental resection of the transverse colon. Histopathological examination confirmed an 11 cm-sized undifferentiated carcinoma of the pancreas with OGCs. Immunohistochemical staining revealed reactivity with pan-cytokeratin in adenocarcinoma component, with vimentin in neoplastic multi-nucleated cells, with CD45/CD68 in OGCs, and with p53 in tumor cells, respectively. The patient had suffered from multiple bone metastases and survived 9 mo after surgery. This case supports the ductal epithelial origin of undifferentiated carcinoma with OGCs and early diagnosis could result in favorable surgical outcomes. Investigations on the surgical role and prognostic factors need to be warranted in this tumor.

  2. Pleomorphic leiomyosarcoma of the adrenal gland with osteoclast-like giant cells.

    PubMed

    Candanedo-González, Fernando A; Vela Chávez, Teresa; Cérbulo-Vázquez, Arturo

    2005-01-01

    Pleomorphic leiomyosarcoma (PLMS) of the adrenal gland is a rare tumor in an unusual location. A primary PLMS of the left adrenal gland is reported in a 59-yr-old Mexican woman who presented progressive flank pain and weight loss. The tumor measured 16 cm in diameter, showed markedly pleomorphic and osteoclast-like giant cells, necrosis, and high mitotic activity (average 15 per 10 high-power fields). The phenotype was supported by light microscopy and corroborated by immunohistochemistry. The neoplastic cells were strongly positive for muscle-specific actin, desmin, vimentin, and p53. They were negative for CD34, HMB45, estrogen receptors, and S-100 protein. The percentage of Ki-67 positive neoplastic cells was 7.6%. DNA content analysis by flow cytometry showed that tumor was diploid, with a high level of apoptosis. Extra-adrenal primary sites of origin were clinically excluded. The patient developed local recurrence and liver metastases 12 mo after initial treatment. She then received adjuvant chemotherapy and radiotherapy and the metastasis was resected. Twenty-four months later, she is alive with no evidence of disease. This is the second case of adrenal PLMS reported. This case exhibited a high histologic grade, aggressive behavior, and p53 overexpression, but diploid DNA content.

  3. Development of fusogenic glass surfaces that impart spatiotemporal control over macrophage fusion: Direct visualization of multinucleated giant cell formation.

    PubMed

    Faust, James J; Christenson, Wayne; Doudrick, Kyle; Ros, Robert; Ugarova, Tatiana P

    2017-06-01

    Implantation of synthetic material, including vascular grafts, pacemakers, etc. results in the foreign body reaction and the formation of multinucleated giant cells (MGCs) at the exterior surface of the implant. Despite the long-standing premise that fusion of mononucleated macrophages results in the formation of MGCs, to date, no published study has shown fusion in context with living specimens. This is due to the fact that optical-quality glass, which is required for the majority of live imaging techniques, does not promote macrophage fusion. Consequently, the morphological changes that macrophages undergo during fusion as well as the mechanisms that govern this process remain ill-defined. In this study, we serendipitously identified a highly fusogenic glass surface and discovered that the capacity to promote fusion was due to oleamide contamination. When adsorbed on glass, oleamide and other molecules that contain long-chain hydrocarbons promoted high levels of macrophage fusion. Adhesion, an essential step for macrophage fusion, was apparently mediated by Mac-1 integrin (CD11b/CD18, αMβ2) as determined by single cell force spectroscopy and adhesion assays. Micropatterned glass further increased fusion and enabled a remarkable degree of spatiotemporal control over MGC formation. Using these surfaces, we reveal the kinetics that govern MGC formation in vitro. We anticipate that the spatiotemporal control afforded by these surfaces will expedite studies designed to identify the mechanism(s) of macrophage fusion and MGC formation with implication for the design of novel biomaterials. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. RNA processing body (P-body) dynamics in mesophyll protoplasts re-initiating cell division.

    PubMed

    Bhullar, Dilbag S; Sheahan, Michael B; Rose, Ray J

    2016-12-07

    The ability of plants to regenerate lies in the capacity of differentiated cells to reprogram and re-enter the cell cycle. Reprogramming of cells requires changes in chromatin organisation and gene expression. However, there has been less focus on changes at the post transcription level. We have investigated P-bodies, sites of post transcriptional gene regulation, in plant cell reprogramming in cultured mesophyll protoplasts; by using a YFP-VARICOSE (YFP-VCSc) translational fusion. We showed an early increase in P-body number and volume, followed by a decline, then a subsequent continued increase in P-body number and volume as cell division was initiated and cell proliferation continued. We infer that plant P-bodies have a role to play in reprogramming the mature cell and re-initiating the cell division cycle. The timing of the first phase is consistent with the degredation of messages no longer required, as the cell transits to the division state, and may also be linked to the stress response associated with division induction in cultured cells. The subsequent increase in P-body formation, with partitioning to the daughter cells during the division process, suggests a role in the cell cycle and its re-initiation in daughter cells. P-bodies were shown to be mobile in the cytoplasm and show actin-based motility which facilitates their post-transcriptional role and partitioning to daughter cells.

  5. Thymoma with loss of keratin expression (and giant cells): a potential diagnostic pitfall.

    PubMed

    Adam, Patrick; Hakroush, Samy; Hofmann, Ilse; Reidenbach, Sonja; Marx, Alexander; Ströbel, Philipp

    2014-09-01

    Due to its profound therapeutic consequences, the distinction between thymoma and T-lymphoblastic lymphoma in needle biopsies is one of the most challenging in mediastinal pathology. One essential diagnostic criterion favouring thymoma is the demonstration of increased numbers of keratin-positive epithelial cells by immunohistochemistry. Loss of keratin expression in neoplastic epithelial cells could lead to detrimental misdiagnoses. We here describe a series of 14 thymic epithelial tumours (11 type B2 and B3 thymomas, 3 thymic carcinomas) with loss of expression of one or more keratins. Cases were analysed for expression of various keratins and desmosomal proteins by immunohistochemistry and immunofluorescence and compared with 45 unselected type B thymomas and 24 thymic carcinomas arranged in a multitissue histological array. All 14 cases showed highly reduced expression of at least one keratin, three cases were completely negative for all keratins studied. Of the 14 cases, 13 showed strong nuclear expression of p63. Expression of desmosomal proteins was preserved, suggesting intact cell contact structures. Loss of expression of broad-spectrum-keratins and K19 was observed in 3 and 5 % of unselected thymomas and in 30 and 60 % of thymic carcinomas. A proportion of keratin-depleted thymomas contained giant cells, reminiscent of thymic nurse cells. Loss of keratin expression in type B2 and B3 thymomas is an important diagnostic pitfall in the differential diagnosis with T-lymphoblastic lymphoma and can be expected in 5 % of cases. A panel of epithelial markers including p63 is warranted to ensure correct diagnosis of keratin-negative mediastinal tumours.

  6. Internal carotid artery stenosis associated with giant cell arteritis: case report and discussion

    PubMed Central

    Zarar, Amna; Zafar, Taqi T; Khan, Asif A; Suri, M Fareed K; Qureshi, Adnan I

    2014-01-01

    Background Cerebrovascular ischemic events associated with giant cell arteritis (GCA) are uncommon and have been reported in 3%–4% of patients. We describe a case report of GCA associated with intracranial stenosis and review various angiographic findings. Case presentation A 66-year-old man presented with worsening headache and vision loss. A recent magnetic resonance angiogram of the head and neck showed multiple intracranial stenosis. Cerebrospinal fluid (CSF) analysis demonstrated increased protein of 135.6 mg/dL, with two white blood cells/µL. No bacteria were observed in the CSF on gram staining, and cultures were negative for bacterial growth. Erythrocyte sedimentation rate was noted to be 14 mm/h, and C-reactive protein was 1.514 mg/L at admission. Human immunodeficiency virus (HIV) and hepatitis panels were negative. On digital subtraction angiography, patient had predominantly narrowing and irregularities in petrous and cavernous segments of the internal carotid arteries bilaterally. The diagnosis of GCA was confirmed by temporal artery biopsy. He was treated with steroids, and a followup angiogram 6 weeks later showed minimal resolution of the angiographic findings. Patient reported complete resolution of headaches and visual loss. Conclusion Bilateral internal carotid arteries stenosis may be seen in patients presenting with typical symptoms of GCA and may persist after steroid treatment despite resolution of clinical symptoms. PMID:25566338

  7. Diffuse-type giant cell tumor/pigmented villonodular synovitis arising in the sacrum: malignant form.

    PubMed

    Oda, Yoshinao; Takahira, Tomonari; Yokoyama, Ryohei; Tsuneyoshi, Masazumi

    2007-09-01

    Diffuse-type giant cell tumor (GCT)/pigmented villonodular synovitis (PVNS) in the axial skeleton or spine is rare. Herein is reported a case of diffuse-type GCT/PVNS involving the sacrum and the fifth lumbar vertebra, in which the patient developed regional lymph node swelling after recurrence. The recurrent tumor was found to have atypical histological features such as spindle cell morphology, cytological atypia and high mitotic rate, which are compatible with the diagnostic criteria of secondary malignant diffuse-type GCT/PVNS. Although the nodal lesions were not sampled histologically, the clinical and histological features indicate that the current case is an example of malignant diffuse-type GCT/PVNS. This case is considered to be the first case of malignant diffuse-type GCT/PVNS in the spine, because no such lesions have been previously reported in the axial skeleton or spine. Careful surveillance should be required for diffuse-type GCT/PVNS arising at unusual site.

  8. Testing Thermophotovoltaic Cells With Black-Body Radiation

    NASA Technical Reports Server (NTRS)

    Lin, James J.; Burger, Dale R.

    1996-01-01

    Method of testing thermophotovoltaic (TPV) cells involves maintaining cells at various temperatures while exposing cells to black-body radiation at various intensities from black-body sources at various other temperatures. Provides for simulation and evaluation of performance under variety of operating conditions and could become standard testing method for government and industry.

  9. Giant cell angiofibroma, a variant of solitary fibrous tumor, of the orbit in a 16-year-old girl.

    PubMed

    Demirci, Hakan; Shields, Carol L; Eagle, Ralph C; Shields, Jerry A

    2009-01-01

    A 16-year-old girl presented with diplopia and gradual-onset, painless proptosis of the left eye. Orbital CT showed a well-circumscribed, enhancing, extraconal mass in the superior orbit, and the surgical excision was performed. Histopathology was interpreted as capillary hemangioma. Five years later, her symptoms recurred, and she was referred to the Oncology Service, Wills Eye Institute. Repeat orbital MRI showed a well-defined, extraconal mass with loculated areas of enhancement in the left orbit superonasally. Complete surgical excision was performed. Histopathologic examination showed benign, patternless spindle-cell proliferation with prominent intrinsic vascularity and multinucleated giant cells, consistent with giant cell angiofibroma, a variant of solitary fibrous tumor. There was intense immunoreactivity for CD34. After 20 months follow-up, there was no recurrence or development of metastasis. Giant cell angiofibroma, a variant of solitary fibrous tumor, is a rare orbital tumor that presents as a well-circumscribed, enhancing mass and can be found in children.

  10. Incidence of discordant temporal artery biopsy in the diagnosis of giant cell arteritis.

    PubMed

    Durling, Bethany; Toren, Andrew; Patel, Vivek; Gilberg, Steven; Weis, Ezekiel; Jordan, David

    2014-04-01

    We investigated the rate of discordant biopsy results (i.e., 1 side negative, 1 side positive) in patients who underwent initial bilateral temporal artery biopsies for suspected giant cell arteritis (GCA). A cohort study. Consecutive patients undergoing temporal artery biopsy were enrolled. Of the 259 patients enrolled, 250 underwent initial bilateral temporal artery biopsies. Positive biopsies were defined based on accepted histologic definitions. Healed arteritis was considered a positive result. Clinical information was collected for all patients using a questionnaire administered by an ophthalmologist. Pathology results, including biopsy length (as measured by the pathologist), and laboratory information (i.e., serum erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP] levels) were collected from digital patient records for statistical analysis. The main outcome was the rate of discordant biopsy in consecutive patients who underwent initial bilateral temporal artery biopsy. Giant cell arteritis was confirmed in 62 (24.2%) of the 250 patients, including 3 patients with biopsies recorded as healed arteritis. The rate of discordant biopsy was 4.4% with 11 unilaterally positive biopsies. There was no statistical difference between the length of the left- and right-sided biopsies in either the unilaterally or bilaterally positive groups (p = 0.13 and p = 0.79, respectively). The average maximum ESR value for the bilateral group (58.7 mm/h) was significantly higher than the average maximum ESR value for the unilateral group (30.7 mm/h, p = 0.03). The average maximum CRP value for the bilateral group was 59.2 mg/L and 28.6 mg/L for the unilateral group (p = 0.30). Discordance between the localization of symptoms and the side of positive biopsy occurred in 3 patients (i.e., 3 patients had left-sided symptoms only, yet a right-sided positive biopsy). The rate of discordant biopsies in patients who underwent initial bilateral temporal artery biopsies was

  11. Resection-reconstruction arthroplasty for giant cell tumor of distal radius

    PubMed Central

    Saikia, Kabul C; Borgohain, Munin; Bhuyan, Sanjeev K; Goswami, Sanjiv; Bora, Anjan; Ahmed, Firoz

    2010-01-01

    Background: Giant cell tumor (GCT) of the distal radius poses problems for reconstruction after resection. Several reconstructive procedures like vascularized and non-vascularized fibular graft, osteo-articular allograft, ceramic prosthesis and megaprosthesis are in use for substitution of the defect in the distal radius following resection. Most authors advocate wrist arthrodesis following resection of distal radius and non vascularized fibular graft. Here we have analyzed the results of aggressive benign GCTs of the distal radius treated by resection and reconstruction arthroplasty using autogenous non-vascularized fibular graft. Materials and Methods: Twenty-four cases of giant cell tumor of the distal radius (mean age 32 years, mean follow-up 6.6 years) treated by en-bloc resection and reconstruction arthroplasty using autogenous non-vascularized ipsilateral fibular graft with a minimum followup of two years have been included in this retrospective study. Nineteen cases were of Campanacci grade III and five were of Grade II recurrence. The mean resected length of the radius was 9.5 (8-12) cm. Routine radiographs and clinical assessments regarding pain, instability, recurrence, hand grip strength and functional status were done at regular intervals and functional results were assessed using (musculoskeletal tumor society) MSTS-87 scoring. Results: Early radiological union at host-graft junction was achieved at mean 12.5 weeks, (range 12-14 weeks) and solid incorporation with callus formation was observed in mean 29 weeks (range 28-32 weeks) in all the cases. Satisfactory range of motion (mean 63%, range 52-78%) of the wrist was achieved in 18 cases. Grip strength compared to the contralateral hand was found to be 67% (range 58-74%). Functional results were excellent in six cases (25%), good in 14 cases (58.3%) and four (16.7%) cases had fair results. Soft tissue recurrence was seen in one patient. The most commonly encountered complication was fibulo

  12. Advantages of Pressurized-Spray Cryosurgery in Giant Cell Tumors of the Bone

    PubMed Central

    Dabak, Nevzat; Göçer, Hasan; Çıraklı, Alper

    2016-01-01

    Background: Giant Cell Tumor is considered a benign, local and aggressive tumor. Although considered a benign bone tumor, it is still the subject of discussion and research because of the associated local bone destruction, as well as high rates of recurrence and distant metastases. Options are being developed for both surgical techniques and adjuvant therapies. Aims: The present study evaluated the administration of cryotherapy via a pressurized-spray technique in giant cell tumors of the bone. Study Design: Cross-sectional study. Methods: The study included 40 patients who were treated with extensive curettage and cryotherapy at various locations during the period from February 2006 to December 2013. Informed consent forms were obtained from the participants and ethics committee approval was taken from the local ethics committee of Ondokuz Mayıs University. The pressurized-spray technique was performed using liquid nitrogen. The patients were evaluated with respect to age, gender, radiological appearance, treatment modality, duration of follow-up, skin problems and recurrence. Results: Twenty-one patients were female; 19 were male. The average age of the patients was 33 years (range: 16–72 years), and the average duration of follow-up was 43 months (range: 12–80 months). The average time from the onset of the complaints to the diagnosis was 6 months (range: 2–12 months). Based on the Campanacci classification: 9 patients were Grade I; 25 patients were Grade II; six patients were Grade III. The lesion was located in the femur in 14 patients, in the tibia in 11 patients, in the radius in 5 patients, in the pelvis in 4 patients, in the fibula in 3 patients, in the metatarsal in 2 patients and in the phalanges of the hand in one patient. One patient had postoperative early fracture. None of the patients had skin problems and infection. Three (7.5%) of the patients had recurrence. Conclusion: It was found that cryotherapy was highly effective in the lesions

  13. Reconstruction of the Midfoot Using a Free Vascularized Fibular Graft After En Bloc Excision for Giant Cell Tumor of the Tarsal Bones: A Case Report.

    PubMed

    Hara, Hitomi; Kawamoto, Teruya; Onishi, Yasuo; Fujioka, Hiroyuki; Nishida, Kotaro; Kuroda, Ryosuke; Kurosaka, Masahiro; Akisue, Toshihiro

    2016-01-01

    We report the case of a 32-year-old Japanese female with a giant cell tumor of bone involving multiple midfoot bones. Giant cell tumors of bone account for approximately 5% of all primary bone tumors and most often arise at the ends of long bones. The small bones, such as those of the hands and feet, are rare sites for giant cell tumors. Giant cell tumors of the small bones tend to exhibit more aggressive clinical behavior than those of the long bones. The present patient underwent en bloc tumor excision involving multiple tarsals and metatarsals. We reconstructed the longitudinal arch of the foot with a free vascularized fibular graft. At the 2-year follow-up visit, bony union had been achieved, with no tumor recurrence. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  14. Unusual chromatin status and organization of the inactive X chromosome in murine trophoblast giant cells.

    PubMed

    Corbel, Catherine; Diabangouaya, Patricia; Gendrel, Anne-Valerie; Chow, Jennifer C; Heard, Edith

    2013-02-01

    Mammalian X-chromosome inactivation (XCI) enables dosage compensation between XX females and XY males. It is an essential process and its absence in XX individuals results in early lethality due primarily to extra-embryonic defects. This sensitivity to X-linked gene dosage in extra-embryonic tissues is difficult to reconcile with the reported tendency of escape from XCI in these tissues. The precise transcriptional status of the inactive X chromosome in different lineages has mainly been examined using transgenes or in in vitro differentiated stem cells and the degree to which endogenous X-linked genes are silenced in embryonic and extra-embryonic lineages during early postimplantation stages is unclear. Here we investigate the precise temporal and lineage-specific X-inactivation status of several genes in postimplantation mouse embryos. We find stable gene silencing in most lineages, with significant levels of escape from XCI mainly in one extra-embryonic cell type: trophoblast giant cells (TGCs). To investigate the basis of this epigenetic instability, we examined the chromatin structure and organization of the inactive X chromosome in TGCs obtained from ectoplacental cone explants. We find that the Xist RNA-coated X chromosome has a highly unusual chromatin content in TGCs, presenting both heterochromatic marks such as H3K27me3 and euchromatic marks such as histone H4 acetylation and H3K4 methylation. Strikingly, Xist RNA does not form an overt silent nuclear compartment or Cot1 hole in these cells. This unusual combination of silent and active features is likely to reflect, and might underlie, the partial activity of the X chromosome in TGCs.

  15. Congenital segmental lymphedema in tuberous sclerosis complex with associated subependymal giant cell astrocytomas treated with Mammalian target of rapamycin inhibitors.

    PubMed

    Prato, Giulia; Mancardi, Maria Margherita; Baglietto, Maria Giuseppina; Janis, Sara; Vercellino, Nadia; Rossi, Andrea; Consales, Alessandro; Raso, Alessandro; Garrè, Maria Luisa

    2014-09-01

    Tuberous sclerosis complex is a genetic, multisystemic disorder characterized by circumscribed benign lesions (hamartomas) in several organs, including brain. This is the result of defects in the TSC1 and/or TSC2 tumor suppressor genes, encoding the hamartin-tuberin complex that inhibits the mammalian target of rapamycin pathway. Specific inhibitors of this pathway have been shown to reduce the volume of subependymal giant cell astrocytomas associated with tuberous sclerosis. Congenital lymphedema is rarely seen in association with tuberous sclerosis, with only a few reported cases. Although this association can be coincidental, the dysgenetic lymphatic system can represent a hamartia as a consequence of gene mutation. We describe a child with congenital lymphedema in tuberous sclerosis and associated subependymal giant cell astrocytoma who experienced lymphangitis under treatment with mammalian target of rapamycin inhibitors. Because our patient did not show worsening of lymphedema, congenital lymphedema does not seem to be a contraindication for this therapy. © The Author(s) 2013.

  16. ON THE EFFECT OF GIANT PLANETS ON THE SCATTERING OF PARENT BODIES OF IRON METEORITE FROM THE TERRESTRIAL PLANET REGION INTO THE ASTEROID BELT: A CONCEPT STUDY

    SciTech Connect

    Haghighipour, Nader; Scott, Edward R. D.

    2012-04-20

    In their model for the origin of the parent bodies of iron meteorites, Bottke et al. proposed differentiated planetesimals, formed in 1-2 AU during the first 1.5 Myr, as the parent bodies, and suggested that these objects and their fragments were scattered into the asteroid belt as a result of interactions with planetary embryos. Although viable, this model does not include the effect of a giant planet that might have existed or been growing in the outer regions. We present the results of a concept study where we have examined the effect of a planetary body in the orbit of Jupiter on the early scattering of planetesimals from the terrestrial region into the asteroid belt. We integrated the orbits of a large battery of planetesimals in a disk of planetary embryos and studied their evolutions for different values of the mass of the planet. Results indicate that when the mass of the planet is smaller than 10 M{sub Circled-Plus }, its effects on the interactions among planetesimals and planetary embryos are negligible. However, when the planet mass is between 10 and 50 M{sub Circled-Plus }, simulations point to a transitional regime with {approx}50 M{sub Circled-Plus} being the value for which the perturbing effect of the planet can no longer be ignored. Simulations also show that further increase of the mass of the planet strongly reduces the efficiency of the scattering of planetesimals from the terrestrial planet region into the asteroid belt. We present the results of our simulations and discuss their possible implications for the time of giant planet formation.

  17. Microsurgical reconstruction in limb salvage due to a giant cell tumor of the distal radius. Case report.

    PubMed

    Sánchez-Torres, L J; de la Parra-Márquez, M L; Cruz-Escalante, A M; Ramírez-Barroso, R; Espinoza-Velazco, A

    2017-01-01

    The giant cell tumor of bone is one of the most controversial neoplasms due to growth patterns that may present. The case reported shows a very aggressive tumor in a classic location, but key to hand function. Rather than treat with radical surgery, was planned and performed a wide resection with an ulnar-carpus arthrodesis and microsurgical reconstruction of the defect throught an anterolateral thigh flap. The multidisciplinary approach of bone neoplasms produce a positive impact on patients.

  18. [Giant cell tumour of bone: a series of 97 cases with a mean follow-up of 12 years].

    PubMed

    Abat, F; Almenara, M; Peiró, A; Trullols, L; Bagué, S; Grácia, I

    2015-01-01

    To describe our series of patients with giant cell tumour of bone with a long-term follow-up to show the results obtained with our treatment protocol. A total of 97 histologically confirmed giant cell tumour of bone were treated in our center between 1982 and 2009. The mean follow-up period was 12 years (2-27 years). The treatment received was determined by the radiological grade based on the Campanacci classification. The series consisted of 53 women (54.6%) and 44 men (54.4%) with a median age of 34.16 years (15-71 years). The data collected was focused on the clinical presentation, location, phase, extension, recurrences, and complications. The treatment most used in Campanacci grades i and ii was intralesional excision with high velocity drilling and filling with a graft. In grades iii that could not be treated with the aforementioned method, it was decided to perform en bloc resection. An overall recurrence rate of around 25.8% was observed. Seven cases (7.2%) presented with a recurrence of the malignancy. The death rate at the end of follow-up was 2.1% (2 cases). Curettage with a high-velocity drill and a bone graft in giant cell tumour of bone Campanacci grades i and ii obtain good results after long-term follow-up. Some grade iii giant cell tumour of bone that cannot be treated with this therapeutic option require en bloc resection and reconstruction. Copyright © 2013 SECOT. Published by Elsevier Espana. All rights reserved.

  19. Central Retinal Artery Occlusion With Subsequent Central Retinal Vein Occlusion in Biopsy-Proven Giant Cell Arteritis.

    PubMed

    Williams, Zoë R; Wang, Xiaofei; DiLoreto, David A

    2016-09-01

    Central retinal artery occlusion with subsequent central retinal vein occlusion in the same eye is a rare entity. We present a 72-year-old man with biopsy-proven giant cell arteritis who developed bilateral arteritic anterior ischemic optic neuropathy and a left central retinal artery occlusion. Subsequently, he developed a left central retinal vein occlusion within 2 weeks of his initial vision loss. His vision did not improve with corticosteroids.

  20. Polymyalgia rheumatica and giant cell arteritis—three challenges—consequences of the vasculitis process, osteoporosis, and malignancy

    PubMed Central

    Emamifar, Amir; Hess, Søren; Gerke, Oke; Hermann, Anne Pernille; Laustrup, Helle; Hansen, Per Syrak; Thye-Rønn, Peter; Marcussen, Niels; Svendstrup, Frank; Gildberg-Mortensen, Rannveig; Bang, Jacob Christian; Farahani, Ziba Ahangarani; Chrysidis, Stavros; Toftegaard, Pia; Andreasen, Rikke Asmussen; le Greves, Sebastian; Andersen, Hanne Randi; Olsen, Rudolf Nezlo; Hansen, Inger Marie Jensen

    2017-01-01

    Abstract Introduction: Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are common inflammatory conditions. The diagnosis of PMR/GCA poses many challenges since there are no specific diagnostic tests. Recent literature emphasizes the ability of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to assess global disease activity in inflammatory diseases. 18F-FDG PET/CT may lead to the diagnosis at an earlier stage than conventional imaging and may also assess response to therapy. With respect to the management of PMR/GCA, there are 3 significant areas of concern as follows: vasculitis process/vascular stiffness, malignancy, and osteoporosis. Methods and analysis: All patients with suspected PMR/GCR referred to the Rheumatology section of Medicine Department at Svendborg Hospital, Denmark. The 4 separate studies in the current protocol focus on: the association of clinical picture of PMR/GCA with PET findings; the validity of 18F-FDG PET/CT scan for diagnosis of PMR/GCA compared with temporal artery biopsy; the prevalence of newly diagnosed malignancies in patients with PMR/GCA, or PMR-like syndrome, with the focus on diagnostic accuracy of 18F-FDG PET/CT scan compared with conventional workup (ie, chest X-ray/abdominal ultrasound); and the impact of disease process, and also steroid treatment on bone mineral density, body composition, and vasculitis/vascular stiffness in PMR/GCA patients. Ethics and dissemination: The study has been approved by the Regional Ethics Committee of the Region of Southern Denmark (identification number: S-20160098) and Danish Data Protection Agency (J.nr 16/40522). Results of the study will be disseminated via publications in peer-reviewed journals, and presentation at national and international conferences. PMID:28658131

  1. High-pressure paint-gun injury of the finger simulating giant cell tumor of tendon sheath.

    PubMed

    Stefanato, Catherine M; Turner, Matthew S; Bhawan, Jag

    2005-02-01

    High-pressure paint guns deliver paint at approximately 3000 pounds per square inch. At this pressure, paint will penetrate the skin and spread quickly through fascial planes and tendon sheaths. The present case is that of a lesion from the finger of a 35-year-old white male in whom a history was initially unavailable. Histologic examination revealed diffuse fibrohistiocytic proliferation and giant cells, with numerous darkly pigmented, uniformly small-sized particles throughout the lesion. The initial impression was that of a giant cell tumor of tendon sheath. However, the pigment particles were negative for Perls stain, and polariscopic examination revealed clear refractile fragments. These findings raised the possibility that the lesion was the result of a traumatic event. On further inquiry, it was revealed that the patient had sustained a high-pressure paint-gun injury 1 year earlier. The simulation, histopathologically, of a giant cell tumor of tendon sheath by a high-pressure paint-gun injury has not, to our knowledge, been reported previously, nor has the histologic finding of small, uniformly sized pigment particles and polarizable refractile fragments in this particular type of injury.

  2. DNA methylation analysis of the temporal artery microenvironment in giant cell arteritis.

    PubMed

    Coit, Patrick; De Lott, Lindsey B; Nan, Bin; Elner, Victor M; Sawalha, Amr H

    2016-06-01

    To investigate the inflammatory response in giant cell arteritis (GCA) by characterising the DNA methylation pattern within the temporal artery microenvironment. Twelve patients with non-equivocal histological evidence for GCA and 12 age-matched, sex-matched and ethnicity-matched controls with normal biopsies were studied. DNA was extracted from the affected portions of temporal artery tissue in patients with GCA and from histologically confirmed normal arteries in controls. Genome-wide DNA methylation status was evaluated using the Illumina Infinium HumanMethylation450 BeadChip Array. Differentially methylated loci between affected and unaffected arterial tissues were identified, and subsequent bioinformatic analysis performed. Immunohistochemistry was used to examine tissue expression patterns in temporal artery biopsies. We identified 1555 hypomethylated CG sites (853 genes) in affected temporal artery tissue from patients with GCA compared with normal controls. Gene ontology enrichment analysis of hypomethylated genes revealed significant representation in T cell activation and differentiation pathways, including both TH1 and TH17 signatures. Our DNA methylation data suggest a role for increased activity of the calcineurin/nuclear factor of activated T cells (NFAT) signalling pathway in GCA, confirmed by immunohistochemistry showing increased expression and nuclear localisation of NFAT1. NFAT signalling downstream targets such as interleukin (IL)-21/IL-21R and CD40L were overexpressed in GCA-affected arteries. Further, proinflammatory genes including TNF, LTA, LTB, CCR7, RUNX3, CD6, CD40LG, IL2, IL6, NLRP1, IL1B, IL18, IL21, IL23R and IFNG were hypomethylated in the cellular milieu of GCA arteries. We characterised the inflammatory response in GCA-affected arteries using 'epigenetic immunophenotyping' and identified molecules and pathways relevant to disease pathogenesis in GCA. Published by the BMJ Publishing Group Limited. For permission to use (where not

  3. Neurotrophins are expressed in giant cell arteritis lesions and may contribute to vascular remodeling.

    PubMed

    Ly, Kim Heang; Régent, Alexis; Molina, Elsa; Saada, Sofiane; Sindou, Philippe; Le-Jeunne, Claire; Brézin, Antoine; Witko-Sarsat, Véronique; Labrousse, François; Robert, Pierre-Yves; Bertin, Philippe; Bourges, Jean-Louis; Fauchais, Anne-Laure; Vidal, Elisabeth; Mouthon, Luc; Jauberteau, Marie-Odile

    2014-11-24

    Giant cell arteritis (GCA) is characterized by intimal hyperplasia leading to ischaemic manifestations that involve large vessels. Neurotrophins (NTs) and their receptors (NTRs) are protein factors for growth, differentiation and survival of neurons. They are also involved in the migration of vascular smooth muscle cells (VSMCs). Our aim was to investigate whether NTs and NTRs are involved in vascular remodelling of GCA. We included consecutive patients who underwent a temporal artery biopsy for suspected GCA. We developed an enzymatic digestion method to obtain VSMCs from smooth muscle cells in GCA patients and controls. Neurotrophin protein and gene expression and functional assays were studied from these VSMCs. Neurotrophin expression was also analysed by immunohistochemistry in GCA patients and controls. Whereas temporal arteries of both GCA patients (n = 22) and controls (n = 21) expressed nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) and sortilin, immunostaining was more intense in GCA patients, especially in the media and intima, while neurotrophin-3 (NT-3) and P75 receptor (P75NTR) were only detected in TA from GCA patients. Expression of TrkB, a BDNF receptor, was higher in GCA patients with ischaemic complications. Serum NGF was significantly higher in GCA patients (n = 28) vs. controls (n = 48), whereas no significant difference was found for BDNF and NT-3. NGF and BDNF enhanced GCA-derived temporal artery VSMC proliferation and BDNF facilitated migration of temporal artery VSMCs in patients with GCA compared to controls. Our results suggest that NTs and NTRs are involved in vascular remodelling of GCA. In GCA-derived temporal artery VSMC, NGF promoted proliferation and BDNF enhanced migration by binding to TrkB and p75NTR receptors. Further experiments are needed on a larger number of VSMC samples to confirm these results.

  4. Utility of temporal artery biopsy samples for genome-wide analysis of giant cell arteritis.

    PubMed

    Cremin, K; Leo, P; Harris, J E; De Smit, E; Bradbury, L; McKelvie, P; Hill, C L; Brown, M A; Hewitt, A W

    2014-01-01

    Giant Cell Arteritis (GCA) is the most common vasculitis affecting the elderly. Archived formalin-fixed paraffin-embedded (FFPE) temporal artery biopsy (TAB) specimens potentially represent a valuable resource for large-scale genetic analysis of this disease. FFPE TAB samples were obtained from 12 patients with GCA. Extracted TAB DNA was assessed by real time PCR before restoration using the Illumina HD FFPE Restore Kit. Paired FFPE-blood samples were genotyped on the Illumina OmniExpress FFPE microarray. The FFPE samples that passed stringent quality control measures had a mean genotyping success of >97%. When compared with their matching peripheral blood DNA, the mean discordant heterozygote and homozygote single nucleotide polymorphisms calls were 0.0028 and 0.0003, respectively, which is within the accepted tolerance of reproducibility. This work demonstrates that it is possible to successfully obtain high-quality microarray-based genotypes FFPE TAB samples and that this data is similar to that obtained from peripheral blood.

  5. Is temporal artery biopsy essential in all cases of suspected giant cell arteritis?

    PubMed

    Grossman, C; Barshack, I; Bornstein, G; Ben-Zvi, I

    2015-01-01

    Temporal artery biopsy (TAB) is performed in cases of suspected giant cell arteritis (GCA), and is the gold-standard for diagnosis of the disease. Current American College of Rheumatology (ACR) classification criteria may aid in the diagnosis of GCA. We aimed to assess whether TAB is essential in all cases of suspected GCA, or whether ACR criteria can replace the need for this procedure in some cases. Retrospective analysis of 216 patients who underwent TAB in a single hospital between 2000 and 2013. Pre-TAB and post-TAB ACR criteria were calculated. Sensitivity and specificity of ACR criteria for the diagnosis of GCA were assessed. Overall, 55 patients had histological evidence of GCA.Out of 161 patients with negative TAB findings, 34 were diagnosed with GCA, and 127 were not diagnosed with GCA. Sensitivity of TAB for the diagnosis of GCA was 61.7%. Sensitivity and specificity of ACR criteria for diagnosis of GCA before performing TAB were 68.5% and 58%, respectively. Sensitivity and specificity of ACR criteria after performing TAB biopsy were 89.8% and 64.5%, respectively. Temporal artery biopsy should be performed in the majority of patients with suspected GCA, and may be obviated only in patients with a pre-TAB ACR score of ≤ 1. In all other cases, when GCA is suspected, ACR criteria should not be a substitute to TAB, as they are not highly specific.

  6. Diagnosis of giant cell arteritis: when should we biopsy the temporal artery?

    PubMed

    Hussain, Omar; McKay, Andrew; Fairburn, Kevin; Doyle, Peter; Orr, Robert

    2016-04-01

    Giant cell arteritis (GCA) can be diagnosed histopathologically by biopsy of the temporal artery, and clinically using the 5-point score of the 1990 American College of Rheumatology (ACR) classification. We aimed to find out whether some patients are referred for biopsy unnecessarily. We audited all referrals (n=100) made to the Department of Oral and Maxillofacial Surgery over 34 months, and used the ACR classification to find out whether patients had had a clinical diagnosis of GCA at referral (ACR score: 3 or more). We then compared them with the result of the biopsy. Of the 100 referred, 98 had a biopsy, and of them, 15 were diagnosed with GCA (2 results were not included). Thirteen of the 15 had already been diagnosed clinically (based on the ACR classification) at referral. Our results gave an ACR specificity of 96% (95% CI: 85% to 99%) but only 20% sensitivity (95% CI: 11% to 32%). There was a linear correlation of high ACR scores with histopathological confirmation. Biopsy is most beneficial when there is a degree of diagnostic uncertainty (ACR: 1 or 2), an atypical presentation, or when steroids may be relatively contraindicated. On the basis of our study, we designed a new referral form for biopsy based on the ACR criteria. Copyright © 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  7. The Thromboembolic Risk in Giant Cell Arteritis: A Critical Review of the Literature

    PubMed Central

    Guida, A.; Tufano, A.; Perna, P.; Moscato, P.; De Donato, M. T.; Finelli, R.; Caputo, D.; Di Minno, M. N. D.

    2014-01-01

    Giant cell arteritis is a systemic vasculitis characterized by granulomatous inflammation of the aorta and its main vessels. Cardiovascular risk, both for arterial and venous thromboembolism, is increased in these patients, but the role of thromboprophylaxis is still debated. It should be suspected in elderly patients suffering from sudden onset severe headaches, jaw claudication, and visual disease. Early diagnosis is necessary because prognosis depends on the timeliness of treatment: this kind of arteritis can be complicated by vision loss and cerebrovascular strokes. Corticosteroids remain the cornerstone of the pharmacological treatment of GCA. Aspirin seems to be effective in cardiovascular prevention, while the use of anticoagulant therapy is controversial. Association with other rheumatological disease, particularly with polymyalgia rheumatica is well known, while possible association with antiphospholipid syndrome is not established. Large future trials may provide information about the optimal therapy. Other approaches with new drugs, such as TNF-alpha blockades, Il-6 and IL-1 blockade agents, need to be tested in larger trials. PMID:24963300

  8. [Giant cell arteritis (temporal arteritis, Horton's arteritis): clinical characteristics and management].

    PubMed

    Rössler, T; Tuchen, S; Hofmüller, W; Wecke, T; Vorwerk, C K; Mawrin, C; Behrens-Baumann, W

    2012-03-01

    Giant cell arteritis can cause diagnostic difficulties due to its heterogeneous symptomatology. Characteristic ophthalmic and systemic symptoms of Horton's disease are discussed. The clinical course is described on the basis of typical patients, which shows that generic symptoms do not have to coexist. The Horton's arteritis potentially represents a systemic vasculitis that requires early diagnosis and treatment in order to avoid dramatic ophthalmic consequences, in worst cases blindness. The erythrocyte sedimentation rate (ESR) represents the most important laboratory parameter. Although temporal artery biopsy remains the only confirmatory procedure for a definite diagnosis, imaging procedures such as sonography, magnetic resonance imaging, ultrasound biomicroscopy are useful in supporting the clinical diagnosis. Highly dosed corticosteroid therapy should always be indicated when suspicious clinical symptoms are present, even without any dramatic laboratory parameter changes. Initial high dosages are indicated up to 1 gram daily depending on the severity of the disease. Subsequently a slow ESR titrated reduction of the dose is necessary under control of inflammation values, symptomatology and side effects. Occasionally a lifelong immunsuppressive therapy is indispensable. The long-term treatment should take place in close cooperation with the general practitioner, rheumatologist, neurologist and if necessary further specialists. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Primary Hyperparathyroidism Misdiagnosed as Giant Cell Bone Tumor of Maxillary Sinus: A Case Report

    PubMed Central

    Aghaghazvini, Leila; Sharifian, Hashem; Rasuli, Bahman

    2016-01-01

    Primary hyperparathyroidism is an endocrine disorder recognized by hyperfunction of parathyroid gland, which can result in persistent bone absorption and brown tumor. Facial involvement of brown tumor is rare and usually involves the mandible. Giant cell tumor ( GCT) is an expansile osteolytic bone tumor which is very similar in clinical, radiological and histological features to brown tumor. Herein, we present a 35-year-old woman with an 11-month history of gradually swelling of the right maxilla and buccal spaces began during pregnancy two years ago. No other clinical or laboratory problems were detected. Postpartum CT scan demonstrated a lytic expansile multi-septated mass lesion containing enhancing areas, which initially described as GCT of the right maxillary sinus following surgery. Four months later, gradual progressive swelling of the bed of tumor was recurred and revised pathological slices were compatible with GCT. Regarding patient recent paresthesia, repeated laboratory tests were performed. Finally, according to laboratory results (elevation of serum calcium and parathyroid hormone), ultrasonographic findings and radioisotope scan (Sestamibi), probable parathyroid mass and brown tumor of maxilla was diagnosed. Pathology confirmed hyperplasia of right inferior parathyroid gland. Our case was thought-provoking due to its interesting clinical presentation and unusual presentation of brown tumor in parathyroid hyperplasia. PMID:27127572

  10. Giant cell tumor locally advanced around the knee: treatment and literature review.

    PubMed

    Rigollino, Ana Valeria; Fernando, Thiago Santos; Tanaka, Marcos Hajime; Souza, Marcello Martins

    2017-01-01

    Giant cell tumor (GCT) is a benign bone tumor with aggressive characteristics. They are more prevalent in the third decade of life and demonstrate a preference for locating in the epiphyseal region of long bones. They have a high local recurrence rate, which depends on the type of treatment and initial tumor presentation. The risk of lung metastases is around 3%. Between October 2010 and August 2014, nine patients diagnosed with locally advanced GCT or with pathological fracture to the knee level underwent surgical treatment. The aim of this study was to evaluate the results of the treatment, particularly with regard to relapse, and to conduct a literature review. There was a predominance of males (77.7%). The most common location was the distal femur. Four patients (44%) developed local recurrence in the first year after surgery, three in distal femur and one in proximal tibia. Of the two patients with pathologic fracture at diagnosis, one of them presented recurrence after five months. The treatment of GCT is still a challenge. The authors believe that the best treatment method is wide resection and reconstruction of bone defects with non-conventional endoprostheses. Patients should be aware and well informed about the possible complications and functional losses that may occur as a result of the surgical treatment chosen and the need for further surgery in the medium and long term.

  11. Acute vision loss and choroidal filling delay in the absence of giant-cell arteritis

    PubMed Central

    Bei, Ling; Lee, Iris; Lee, Michael S; Van Stavern, Greg P; McClelland, Collin M

    2016-01-01

    Giant-cell arteritis (GCA) is a visually devastating disease that often progresses to severe bilateral vision loss if untreated. Diagnosis of GCA is made challenging by the protean nature of the disease and the lack of a simple test that is both highly sensitive and specific. Choroidal filling delay on fluorescein angiography (FA) has been touted as a highly characteristic feature of GCA-related vision loss, although knowledge of both the sensitivity and specificity of this finding remains unproven. We report our experience of delayed choroidal filling on FA in a series of seven patients referred to an academic neuro-ophthalmology practice due to concern for GCA. Despite the FA findings, our examination, diagnostic testing, and long-term follow-up excluded the diagnosis of GCA in all cases, suggesting that choroidal perfusion abnormalities may occur in the absence of GCA. When evaluating a patient for acute vision loss, the astute clinician must remain cognizant of the limitations of FA in the diagnosis of GCA. PMID:27695279

  12. Anti-CD20 treatment of giant cell hepatitis with autoimmune hemolytic anemia.

    PubMed

    Paganelli, Massimiliano; Patey, Natacha; Bass, Lee M; Alvarez, Fernando

    2014-10-01

    Giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA) is a rare autoimmune disease of infancy characterized by severe liver disease associated with Coombs-positive hemolytic anemia. We recently showed that GCH-AHA is probably caused by a humoral immune mechanism. Such data support the use of rituximab, an anti-CD-20 monoclonal antibody specifically targeting B lymphocytes, as a treatment for GCH-AHA. We describe here the detailed clinical evolution of 4 children with GCH-AHA who showed a complete response to rituximab. All patients shared a severe course of the disease with poor control on standard and aggressive immunosuppression. Rituximab was well tolerated, and no side effects or infections were registered. Several doses were needed to induce remission, and 5 to 11 additional maintenance injections were necessary in the 2 more severe cases. Weaning from corticosteroids was achieved in all subjects. A steroid-sparing effect was noted in the 3 children who started rituximab early in the course of the disease. Overall, we show here that there is a strong rationale for treating GCH-AHA with rituximab. Early treatment could reduce the use of corticosteroids. Nevertheless, short-term steroids should be initially associated with rituximab to account for autoantibodies' half-life. Repeated injections are needed to treat and prevent relapses, but the best frequency and duration of treatment remain to be defined.

  13. Clinical characteristics and prognoses of six patients with multicentric giant cell tumor of the bone

    PubMed Central

    Liu, Chenglei; Tang, Yawen; Li, Mei; Jiao, Qiong; Zhang, Huizhen; Yang, Qingcheng; Yao, Weiwu

    2016-01-01

    Multicentric giant cell tumor of the bone (MGCT) is a rare entity whose radiographic, pathological and biological features remain confusing. We retrospectively reviewed six patients (1 male, 5 female; average age, 22.33 years) treated for confirmed MGCT between 2001 and 2015. The patients' clinical information, images from radiographs (n = 14), CT (n = 13), MRI (n = 8), bone scintigraphy (n = 1) and PET-CT (n = 2), as well as histologic features, treatment and prognosis were analyzed. A total of 17 lesions were detected: 4 around the knee joint, 3 in the greater trochanter and head of the femur, 5 in the small bones of the feet, and 2 in flat bones. All these lesions occurred in an ipsilateral extremity. One patient had Paget's disease. On radiographs and CT, 12 lesions exhibited sclerotic margins or patchy sclerosis, 8 showed cortical discontinuity, and 5 showed soft tissue masses. On histopathology, 8 lesions showed signs of sarcomatous transformation and one had transformed into osteosarcoma. Ten lesions in 4 patients were initially treated with surgery, and 3 showed local recurrence. Seven lesions in 3 patients were treated with denosumab. All the patients are currently stable without metastasis. These results suggest MGCT tends to occur in uncommon sites with sclerosis. Because these lesions can be aggressive, patients should be carefully monitored for the recurrence or formation of other lesions, especially in an ipsilateral extremity. PMID:27823978

  14. Giant cell arteritis in a neuro-ophthalmology clinic in Saskatoon, 1998-2003.

    PubMed

    Ramstead, Cory L; Patel, Anil D

    2007-04-01

    We present a retrospective review of all biopsy-positive cases of giant cell arteritis (GCA) presenting to a neuro-ophthalmology practice in Saskatoon, Saskatchewan. Records of 141 consecutive patients who underwent temporal artery biopsy at the Saskatoon Eye Centre from July 1998 through June 2003 were reviewed. Patients that were biopsy-positive for GCA were studied and an estimated regional incidence was calculated. Study variables included age at diagnosis, sex, ethnicity, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level. Of 141 patients, 37 (26%) had a positive biopsy result for GCA; 11 underwent a second biopsy for a total of 152 biopsies. The average age of the biopsy-positive patients was 76.5 (SD 8.2) years, and the female-to-male ratio was 2.4:l. There were 35 patients (95%) of European descent and 2 patients (5%) of Aboriginal descent. Twenty-three patients had both ESR and CRP testing done before starting steroids. The ESR was elevated in 19 (83%) and the CRP in 22 (96%). The estimated incidence of GCA for Saskatoon and area was 9.4 per 100,000 for people over the age of 50 years. GCA occurs primarily in people of European descent; however, it can affect North American people of Aboriginal descent. Sensitivity for the detection of GCA is higher in CRP than in ESR. The estimated incidence of GCA in Saskatoon and surrounding referral area is moderate compared with other northern areas.

  15. Tenosynovial giant cell tumour (pigmented villonodular synovitis-)-like changes in periprosthetic interface membranes.

    PubMed

    Söder, Stephan; Sesselmann, Stefan; Aigner, Thomas; Oehler, Stephan; Agaimy, Abbas

    2016-02-01

    Tenosynovial giant cell tumour (TSGCT; synonym, pigmented villonodular synovitis (PVNS)) is a rare low-grade mesenchymal neoplasm of either intra-articular or extra-articular origin. The etiopathogenesis of TSGCT is still uncertain, but recent studies showed a translocation involving colony-stimulating factor 1 (CSF-1) gene in a subset of cases. Histological features mimicking TSGCT can sometimes be encountered in periprosthetic interface membranes. To investigate the frequency and morphologic spectrum of this phenomenon, we conducted a systematic analysis of 477 periprosthetic interface membranes and performed immunohistochemical analysis on a subset of lesions compared to genuine TSGCT. In 26 of 477 periprosthetic membrane samples (5 %), at least some TSGCT-like features were found and 18 cases (4 %) strongly resembled it. Wear particles were detected in 100 % of the TSGCT-like lesions but only in 63.3 % of the whole cohort of periprosthetic membranes (p value <0.001). Immunohistochemistry comparing true TSGCT and TSGCT-like membranes showed similar inflammatory infiltrates with slightly elevated CD3+/CD8+ T lymphocytes and a slightly higher proliferation index in TSGCT samples. In conclusion, TSGCT-like changes in periprosthetic membranes likely represent exuberant fibrohistiocytic inflammatory response induced by wear particles and should be distinguished from genuine (neoplastic) TSGCT. Although TSGCT and TSGCT-like periprosthetic membranes represent different entities, their comparable morphology might reflect analogous morphogenesis.

  16. ZNF687 Mutations in Severe Paget Disease of Bone Associated with Giant Cell Tumor.

    PubMed

    Divisato, Giuseppina; Formicola, Daniela; Esposito, Teresa; Merlotti, Daniela; Pazzaglia, Laura; Del Fattore, Andrea; Siris, Ethel; Orcel, Philippe; Brown, Jacques P; Nuti, Ranuccio; Strazzullo, Pasquale; Benassi, Maria Serena; Cancela, M Leonor; Michou, Laetitia; Rendina, Domenico; Gennari, Luigi; Gianfrancesco, Fernando

    2016-02-04

    Paget disease of bone (PDB) is a skeletal disorder characterized by focal abnormalities of bone remodeling, which result in enlarged and deformed bones in one or more regions of the skeleton. In some cases, the pagetic tissue undergoes neoplastic transformation, resulting in osteosarcoma and, less frequently, in giant cell tumor of bone (GCT). We performed whole-exome sequencing in a large family with 14 PDB-affected members, four of whom developed GCT at multiple pagetic skeletal sites, and we identified the c.2810C>G (p.Pro937Arg) missense mutation in the zinc finger protein 687 gene (ZNF687). The mutation precisely co-segregated with the clinical phenotype in all affected family members. The sequencing of seven unrelated individuals with GCT associated with PDB (GCT/PDB) identified the same mutation in all individuals, unravelling a founder effect. ZNF687 is highly expressed during osteoclastogenesis and osteoblastogenesis and is dramatically upregulated in the tumor tissue of individuals with GCT/PDB. Interestingly, our preliminary findings showed that ZNF687, indicated as a target gene of the NFkB transcription factor by ChIP-seq analysis, is also upregulated in the peripheral blood of PDB-affected individuals with (n = 5) or without (n = 6) mutations in SQSTM1, encouraging additional studies to investigate its potential role as a biomarker of PDB risk.

  17. Giant cell tumor of the patella with a secondary aneurysmal bone cyst: A case report

    PubMed Central

    SONG, MINGZHI; DAI, WEI; SUN, RAN; LIANG, HONGFENG; LIU, BINGWU; WU, YUXUAN; MA, KAI; LU, MING

    2016-01-01

    The substance of the patella is an uncommon location for tumor occurrence and development. The present study reports a case of giant cell tumor (GCT) of the patella, combined with an aneurysmal bone cyst (ABC). To the best of our knowledge, this is the second report of GCT with ABC published in English. GCT is the most common type of benign tumor. Secondary ABC is frequently associated with GCT, but this symbiotic tumor rarely occurs in the patella. A 27-year-old male patient was examined at the outpatient clinic, and clinicopathological characteristics of the tumor were observed. X-ray and computed tomography (CT) scans revealed a lytic lesion located in the center of the right patella. Curettage, followed by autogenic and allograft bone grafting, was performed. Histopathologically, the lesion was diagnosed as a GCT with secondary ABC. No recurrence or metastasis was identified during the 1-year follow-up period. The present study reports a case of GCT with secondary ABC, and discusses the rare location and histopathological type of this tumor, in order to improve diagnosis and treatment of patellar tumors in general. PMID:27313738

  18. Everolimus: in patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex.

    PubMed

    Curran, Monique P

    2012-02-01

    Everolimus is an orally administered inhibitor of the mammalian target of rapamycin (mTOR). Everolimus (starting dosage 3.0 mg/m(2)) was associated with a significant reduction in the volume of the largest subependymal giant cell astrocytoma (SEGA) in 28 patients aged ≥3 years with tuberous sclerosis complex (TSC) in a phase II trial (C2485). At 6 months, 32% of patients treated with everolimus had a ≥50% reduction in the volume of their largest SEGA lesion (assessed via an independent central radiology review); 75% had a ≥30% reduction. No patients developed new lesions. During the extension phase of this trial (median duration 34 months), the reduction in SEGA volume was maintained, with no everolimus recipient requiring surgery or other therapy for SEGA or hydrocephalus. In a phase III trial (EXIST-1) in 117 patients with SEGA associated with TSC, 35% of everolimus recipients (starting dosage 4.5 mg/m(2)) versus none of the placebo recipients (p < 0.0001) had an overall response (a reduction in the sum of all target SEGA volumes of ≥50% relative to baseline, nonworsening of non-target SEGA lesions, no new SEGA lesions, and no new/worsening hydrocephalus). Everolimus was generally well tolerated in patients with SEGA associated with TSC; most drug-related adverse reactions were mild to moderate in severity.

  19. Lower extremity vasculitis in giant cell arteritis: important differential diagnosis in patients with lower limb claudication.

    PubMed

    Sigl, Martin; Hsu, Eric; Scheffel, Hans; Haneder, Stefan; Rümenapf, Gerhard; Amendt, Klaus

    2014-09-01

    Most patients with peripheral arterial disease suffer from arteriosclerosis, the prevalence of which increases with age. In some of these patients, however, the ischemic symptoms are not caused by stenotic arteriosclerosis, but by large vessel giant cell arteritis (LV-GCA), a disease also predominantly affecting patients of the older generation. Identifying large vessel vasculitis is a challenge for all physicians caring for patients with peripheral artery disease. The results of invasive treatment such as bypass surgery and angioplasty of inflammatory vascular lesions differ fundamentally from those of patients with atherosclerosis. Duplex ultrasound is a widely available diagnostic method for examining patients with lower limb claudication and pathological ankle-/toe- brachial index or pulse volume recording with or without exercise. Knowledge of characteristic sonographic findings suspicious about large vessel vasculitis is essential for a differential diagnosis of vasculitis versus atherosclerosis. In addition to clinical and laboratory findings, further imaging techniques, e.g. contrast-enhanced computed tomography, magnetic resonance imaging or a combination of positron emission tomography and computed tomography (PET-CT) can provide information on further vessel involvement and inflammatory activity. The present study focuses on diagnostic imaging of LV-GCA in patients presenting with claudication, illustrated by a series of cases.

  20. Pediatric giant cell glioblastoma: New insights into a rare tumor entity

    PubMed Central

    Karremann, Michael; Butenhoff, Sandra; Rausche, Ulrike; Pietsch, Torsten; Wolff, Johannes E. A.; Kramm, Christof M.

    2009-01-01

    Little is known about giant cell glioblastoma (GCG) in pediatric patients. The present study identified 18 pediatric patients with centrally reviewed GCG from the HIT-GBM database of the Gesellschaft für Paediatrische Onkologie und Haematologie in Germany, Austria, and Switzerland. Clinical and epidemiological data were compared with those of 178 pediatric patients with centrally reviewed glioblastoma multiforme (GBM) from the same database. In this unique series, median age, male preference, and median clinical history did not differ significantly between pediatric GCG and GBM patients. GCG showed a stronger predilection for cerebral hemispheres than did GBM, which may only partly explain the higher percentage of gross total tumor resections in GCG patients. Most surprising, the widely distributed hypothesis that GCG may imply a better prognosis than GBM could not be substantiated for our pediatric series. Future studies with larger patient numbers and molecular pathological analyses are still needed to corroborate the present findings and further elucidate the biology of GCG in children. PMID:19050301

  1. Wide excision and ulno-carpal arthrodesis for primary aggressive and recurrent giant cell tumours

    PubMed Central

    Bansal, M.; Jandhyala, R.; Sharma, H.; Amin, P.; Pandit, J. P.

    2007-01-01

    Twenty-five patients underwent wide resection of the distal radial giant cell tumours (GCTs) followed by ulno-carpal arthrodesis. There were 15 male and ten female patients, with an average age of 21.5 years. Tumours included ten primary aggressive and 15 recurrent GCTs. Mean follow up was 2.4 years. Pain, swelling and reduced range of movement (ROM) were noted. Average time to fusion was 7.6 months. Five patients had persistent pain in the proximal forearm. Grip strength was 65% compared to the uninvolved side. Two patients had superficial wound infection, two underwent additional bone grafting and three implant removals due to hardware prominence were carried out. There was no evidence of carpal instability or arthritis on clinical or radiological examination at the time of final follow up. Fusion of the carpus to the ulna is a simple method of producing a painless stable wrist, though at the expense of mobility. The procedure allows wide resection with a lower rate of recurrence. Pain in the proximal forearm seems to persist for 3 to 4 months only to improve at subsequent follow up. The procedure provides a valid option for the management of primary aggressive and recurrent GCTs of distal radius. PMID:17643243

  2. Giant-cell tumor: analysis on the importance of early diagnosis and the epidemiological profile☆

    PubMed Central

    de Carvalho Diniz Ferraz, Diego Firmino; Torres dos Santos, César Augusto; Farias Costa, Victor Hugo; Gonçalves Souza, Antônio Marcelo; Gomes Lima, Paulo Rogerio

    2016-01-01

    Objective This study aimed to ascertain the relationship between early diagnosis of giant-cell tumors (GCT) and their prognosis, by correlating the time of symptom onset with the staging of the injury (through the Campanacci classification at the time of diagnosis), and with the type of treatment. The secondary objective of the study was to outline the epidemiological profile of patients with GCT in the region where the data were gathered, and to compare them with data in the literature. Methods The authors present an evaluation on 61 patients diagnosed with bone GCT, with regard to the site of involvement, age, initial symptoms, time of symptom onset, classification and type of treatment, among patients attended between May 1994 and August 2009. Results The threshold indicated as the limit for Campanacci stage I tumors to be the commonest diagnosis, with a 98.2% chance that the treatment would be non-aggressive, was 2 months after symptom onset. This finding was statistically significant (p = 0.017). Every additional month increased the chance that a patient would be diagnosed with an advanced-stage tumor by 10.94%, in relation to the chances of having the other two stages of the tumor. Conclusion The study result not only suggests that the alternative hypothesis that the earlier the diagnosis of GCT is, the less severe the lesion will be, has been confirmed; but also especially predicts the relationship between the time of symptom appearance and the severity of the tumor. PMID:26962501

  3. Management of giant cell arteritis: Recommendations of the French Study Group for Large Vessel Vasculitis (GEFA).

    PubMed

    Bienvenu, B; Ly, K H; Lambert, M; Agard, C; André, M; Benhamou, Y; Bonnotte, B; de Boysson, H; Espitia, O; Fau, G; Fauchais, A-L; Galateau-Sallé, F; Haroche, J; Héron, E; Lapébie, F-X; Liozon, E; Luong Nguyen, L B; Magnant, J; Manrique, A; Matt, M; de Menthon, M; Mouthon, L; Puéchal, X; Pugnet, G; Quemeneur, T; Régent, A; Saadoun, D; Samson, M; Sène, D; Smets, P; Yelnik, C; Sailler, L; Mahr, A

    2016-03-01

    Management of giant cell arteritis (GCA, Horton's disease) involves many uncertainties. This work was undertaken to establish French recommendations for GCA management. Recommendations were developed by a multidisciplinary panel of 33 physicians, members of the French Study Group for Large Vessel Vasculitis (Groupe d'étude français des artérites des gros vaisseaux [GEFA]). The topics to be addressed, selected from proposals by group members, were assigned to subgroups to summarize the available literature and draft recommendations. Following an iterative consensus-seeking process that yielded consensus recommendations, the degree of agreement among panel members was evaluated with a 5-point Likert scale. A recommendation was approved when ≥ 80% of the voters agreed or strongly agreed. The 15 retained topics resulted in 31 consensus recommendations focusing on GCA nomenclature and classification, the role of temporal artery biopsy and medical imaging in the diagnosis, indications and search modalities for involvement of the aorta and its branches, the glucocorticoid regimen to prescribe, treatment of complicated GCA, indications for use of immunosuppressants or targeted biologic therapies, adjunctive treatment measures, and management of relapse and recurrence. The recommendations, which will be updated regularly, are intended to guide and harmonize the standards of GCA management. Copyright © 2016 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  4. The thromboembolic risk in giant cell arteritis: a critical review of the literature.

    PubMed

    Guida, A; Tufano, A; Perna, P; Moscato, P; De Donato, M T; Finelli, R; Caputo, D; Di Minno, M N D

    2014-01-01

    Giant cell arteritis is a systemic vasculitis characterized by granulomatous inflammation of the aorta and its main vessels. Cardiovascular risk, both for arterial and venous thromboembolism, is increased in these patients, but the role of thromboprophylaxis is still debated. It should be suspected in elderly patients suffering from sudden onset severe headaches, jaw claudication, and visual disease. Early diagnosis is necessary because prognosis depends on the timeliness of treatment: this kind of arteritis can be complicated by vision loss and cerebrovascular strokes. Corticosteroids remain the cornerstone of the pharmacological treatment of GCA. Aspirin seems to be effective in cardiovascular prevention, while the use of anticoagulant therapy is controversial. Association with other rheumatological disease, particularly with polymyalgia rheumatica is well known, while possible association with antiphospholipid syndrome is not established. Large future trials may provide information about the optimal therapy. Other approaches with new drugs, such as TNF-alpha blockades, Il-6 and IL-1 blockade agents, need to be tested in larger trials.

  5. Giant radiolytic dissolution rates of aqueous ceria observed in-situ by liquid-cell TEM.

    PubMed

    Asghar, Muhammad Sajid Ali; Inkson, Beverley J; Moebus, Guenter

    2017-03-09

    Dynamics of cerium oxide nanoparticle aqueous corrosion are revealed in-situ. We use innovative liquid-cell transmission electron microscopy (TEM) combined with deliberate high-intensity electron-beam irradiation of nanoparticle suspensions. This enables life video-recording of materials reactions in liquid, with nm-resolution. We introduce image-quantification to measure detailed rates of dissolution as a function of time and particle size to be compared with literature data. Giant dissolution rates, exceeding any previous reports for chemical dissolution rates at room temperature by many orders of magnitude, are discovered. Reasons for accelerated dissolution are outlined, including the importance of radiolysis of water preceding ceria-attack. Electron-water interaction generates radicals, ions and hydrated electrons, which assist in hydration and reductive dissolution of oxide minerals. The presented methodology has the potential to become a novel accelerated testing procedure to compare multiple nanoscale materials for relative aqueous durability. The ceria-water system is of crucial importance for the fields of catalysis, abrasive polishing, environmental remediation, and as simulant for actinide-oxide behaviour in contact with liquid for nuclear engineering.

  6. Aneurysmal bone cyst secondary to a giant cell tumor of the patella: A case report.

    PubMed

    Yu, Xiaolong; Guo, Runsheng; Fan, Congliang; Liu, Hucheng; Zhang, Bin; Nie, Tao; Tu, Y I; Dai, Min

    2016-02-01

    The patella is an unusual location for primary and metastatic bone tumors to develop. The most frequently encountered primary osteolytic lesions at the patella include giant cell tumors of the bone (GCT), chondroblastoma and aneurysmal bone cysts (ABC). However, the presentation of an ABC originating secondary to a GCT at the patella is rare. The present study describes such a case in a 46-year-old female. The differential diagnosis of the condition was extensive. The patient underwent curettage and the addition of bone cement to fill the defect. Pathological analysis of the resected tissue demonstrated that the lesion was consistent with an ABC forming secondary to a GCT. A 3-month follow-up was completed subsequent to the surgery, with a computed tomography scan demonstrating no evidence of recurrence. However, frequent and continuous observations of the patient following diagnosis are planned in order to evaluate the long-term efficacy of the surgical treatment. To the best of our knowledge, the present study describes the third reported case in the literature of this rare, double synchronous, benign tumor located at the patella.

  7. Temporal artery biopsy in the diagnosis of giant cell arteritis: Bigger is not always better.

    PubMed

    Papadakis, Marios; Kaptanis, Sarantos; Kokkori-Steinbrecher, Aikaterini; Floros, Nikolaos; Schuster, Frauke; Hübner, Gunnar

    2017-09-01

    Accurate early giant cell arteritis (GCA) diagnosis can be established through temporal artery biopsy (TAB). We herein investigate the relationship between specimen length and positive TAB result in a tertiary-care hospital in Germany during a 8-year period. Secondarily, we studied the relationships of specific epidemiological and laboratory parameters with positive TABs. We retrospectively reviewed the medical records of all patients with suspected GCA, who underwent TAB in our institution. The total sample consisted of 116 patients with a mean age of 76.1 (SD 7.7) years. Mean specimen length post-fixation was 0.94 cm (SD 0.49). The TAB(+) group consisted of 64 patients (55.2%). The specimen length was comparable in the two groups (0.96 cm vs 0.91 cm, p = 0.581). Twenty six TAB(+) patients (41%) had a post-fixation specimen longer than 1 cm, comparable with the respective percentage in the TAB(-) group (42%, p = 1). All laboratory tests performed were statistically significantly different in the two groups. We conclude that TAB length is not associated with the TAB diagnostic yield in patients with clinical suspicion of GCA. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Pyogenic Granuloma/Peripheral Giant-Cell Granuloma Associated with Implants

    PubMed Central

    Jané-Salas, Enric; Albuquerque, Rui; Font-Muñoz, Aura; González-Navarro, Beatríz; Estrugo Devesa, Albert; López-López, Jose

    2015-01-01

    Introduction. Pyogenic granuloma (PG) and peripheral giant-cell granuloma (PGCG) are two of the most common inflammatory lesions associated with implants; however, there is no established pathway for treatment of these conditions. This paper aims to illustrate the successful treatment of PG and PGCG and also report a systematic review of the literature regarding the various treatments proposed. Methods. To collect relevant information about previous treatments for PG and PGCG involving implants we carried out electronic searches of publications with the key words “granuloma”, “oral”, and “implants” from the last 15 years on the databases Pubmed, National Library of Medicine's Medline, Scielo, Scopus, and Cochrane Library. Results. From the electronic search 16 case reports were found showing excision and curettage as the main successful treatment. As no clinical trials or observational studies were identified the authors agreed to present results from a review perspective. Conclusion. This is the largest analysis of PG and PGCG associated with implants published to date. Our review would suggest that PGCG associated with implants appears to have a more aggressive nature; however the level of evidence is very limited. Further cohort studies with representative sample sizes and standard outcome measures are necessary for better understanding of these conditions. PMID:26697068

  9. An Unusual and Complicated Course of a Giant Cell Tumor of the Capitate Bone

    PubMed Central

    2016-01-01

    A 51-year-old female patient presented with a carpal giant cell tumor (GCT) of the right capitate bone. The lesion was initially misdiagnosed as having an osteomyelitis. First, the diagnosis of a benign GCT was confirmed by histological examination. Second, an intralesional curettage and packing of the cavity with cancellous iliac crest bone grafts combined with a fusion of the third carpometacarpal (CMC III) joint were carried out. Third, due to a secondary midcarpal osteoarthritis and a secondary scaphoid nonunion, the CMC III joint fusion plate was removed and the midcarpal joint completely excised. Fourth, in the absence of recurrence of GCT, a four-corner fusion (4CF) with a corticocancellous iliac crest bone graft and complete excision of the scaphoid bone had to be performed. Fifth, a total wrist arthroplasty (TWA) was performed due to hardware failure of 4CF with migration of a headless compression screw into radiocarpal joint which led to erosion of articular surface of the distal radius. At the 3-year follow-up that includes a 1-year follow-up after TWA, there was no recurrence of GCT, and the TWA was not failed. The patient reported that she would have the motion-preserving TWA again. PMID:27847665

  10. Treating giant cell tumours with curettage, electrocautery, burring, phenol irrigation, and cementation.

    PubMed

    Moon, Myung-Sang; Kim, Sung-SooS S; Moon, Jeong-Lim; Kim, Sung-Sim; Moon, Hanlim

    2013-08-01

    PURPOSE. To report on 23 patients with giant cell tumour (GCT) of the femur or tibia treated with curettage, electrocautery, burring, phenol irrigation, and cementation. METHODS. Records of these 14 men and 9 women aged 22 to 38 (mean, 31) years were reviewed. The most common site involved was the distal femur (n=13), followed by proximal tibia (n=8), proximal femur (n=1), and distal tibia (n=1). The lesions were classified as grade I (n=3), grade II (n=18), and grade III (n=2). Based on histology, the tumour stage was classified as grade I (n=5) and grade II (n=18). Two of these patients had recurrences, which were initially treated with simple curettage and bone grafting of the distal femur and distal tibia. RESULTS. The mean follow-up period was 5.7 (range, 2.5-10.1) years. 14 of the 23 patients were followed up for over 10 years. No patient developed any local recurrence, remote metastasis, or complication related to surgery or adjuvant therapy. CONCLUSION. Combined treatment entailing curettage, electrocautery, burring, phenol irrigation, and cementation was effective in treating GCT of bone.

  11. ZNF687 Mutations in Severe Paget Disease of Bone Associated with Giant Cell Tumor

    PubMed Central

    Divisato, Giuseppina; Formicola, Daniela; Esposito, Teresa; Merlotti, Daniela; Pazzaglia, Laura; Del Fattore, Andrea; Siris, Ethel; Orcel, Philippe; Brown, Jacques P.; Nuti, Ranuccio; Strazzullo, Pasquale; Benassi, Maria Serena; Cancela, M. Leonor; Michou, Laetitia; Rendina, Domenico; Gennari, Luigi; Gianfrancesco, Fernando

    2016-01-01

    Paget disease of bone (PDB) is a skeletal disorder characterized by focal abnormalities of bone remodeling, which result in enlarged and deformed bones in one or more regions of the skeleton. In some cases, the pagetic tissue undergoes neoplastic transformation, resulting in osteosarcoma and, less frequently, in giant cell tumor of bone (GCT). We performed whole-exome sequencing in a large family with 14 PDB-affected members, four of whom developed GCT at multiple pagetic skeletal sites, and we identified the c.2810C>G (p.Pro937Arg) missense mutation in the zinc finger protein 687 gene (ZNF687). The mutation precisely co-segregated with the clinical phenotype in all affected family members. The sequencing of seven unrelated individuals with GCT associated with PDB (GCT/PDB) identified the same mutation in all individuals, unravelling a founder effect. ZNF687 is highly expressed during osteoclastogenesis and osteoblastogenesis and is dramatically upregulated in the tumor tissue of individuals with GCT/PDB. Interestingly, our preliminary findings showed that ZNF687, indicated as a target gene of the NFkB transcription factor by ChIP-seq analysis, is also upregulated in the peripheral blood of PDB-affected individuals with (n = 5) or without (n = 6) mutations in SQSTM1, encouraging additional studies to investigate its potential role as a biomarker of PDB risk. PMID:26849110

  12. Lethal giant larvae-1 deficiency enhances the CD8(+) effector T-cell response to antigen challenge in vivo.

    PubMed

    Ramsbottom, Kelly M; Sacirbegovic, Faruk; Hawkins, Edwin D; Kallies, Axel; Belz, Gabrielle T; Van Ham, Vanessa; Haynes, Nicole M; Durrant, Michael J; Humbert, Patrick O; Russell, Sarah M; Oliaro, Jane

    2016-03-01

    Lethal giant larvae-1 (Lgl-1) is an evolutionary conserved protein that regulates cell polarity in diverse lineages; however, the role of Lgl-1 in the polarity and function of immune cells remains to be elucidated. To assess the role of Lgl-1 in T cells, we generated chimeric mice with a hematopoietic system deficient for Lgl-1. Lgl-1 deficiency did not impair the activation or function of peripheral CD8(+) T cells in response to antigen presentation in vitro, but did skew effector and memory T-cell differentiation. When challenged with antigen-expressing virus or tumor, Lgl-1-deficient mice displayed altered T-cell responses. This manifested in a stronger antiviral and antitumor effector CD8(+) T-cell response, the latter resulting in enhanced control of MC38-OVA tumors. These results reveal a novel role for Lgl-1 in the regulation of virus-specific T-cell responses and antitumor immunity.

  13. Giant cell tumors of the spine: has denosumab changed the treatment paradigm?

    PubMed

    Goldschlager, Tony; Dea, Nicolas; Boyd, Michael; Reynolds, Jeremy; Patel, Shreyaskumar; Rhines, Laurence D; Mendel, Ehud; Pacheco, Marina; Ramos, Edwin; Mattei, Tobias A; Fisher, Charles G

    2015-05-01

    OBJECT Giant cell tumors (GCTs) of the spine are rare and complex to treat. They have a propensity for local recurrence and the potential to metastasize. Treatment is currently surgical and presents unique challenges due to the proximity of neural structures and the need for reconstruction. Denosumab has been shown in clinical trials to be an effective treatment for GCT, but has not yet been studied specifically in GCT of the spine or as a surgical adjunct. To the authors' knowledge this is the first such reported series. METHODS A multicenter, prospective series of 5 patients with GCT of the spine treated with denosumab were included. Patient demographic data, oncological history, neurological status, tumor staging, treatment details and adverse events, surgical procedure, complications, radiological and histological responses, and patient outcome were analyzed. RESULTS All patients were women, with a mean age of 38 years, and presented with pain; 2 patients had additional neurological signs and symptoms. The mean duration of symptoms was 62 weeks. No patient had a prior tumor or metastatic disease at presentation. All patients had Enneking Stage III tumors and were treated with monthly cycles of 120 mg of denosumab, with initial additional loading doses on Days 8 and 15. Patients were given daily supplements of calcium (500 mg) and vitamin D (400 IU). There were no denosumab-related adverse events. All patients had a radiological response to denosumab. One patient failed to have a histological response to denosumab, with > 90% of tumor cells found to be viable on histological investigation. CONCLUSIONS This study reports the early experience of using denosumab in the treatment of spinal GCT. The results demonstrate a clinically beneficial radiological response and an impressive histological response in most but not all patients. Further experience with denosumab and longer patient follow-up is required. Denosumab has the potential to change the treatment paradigm

  14. An observational study of giant cell interstitial pneumonia and lung fibrosis in hard metal lung disease.

    PubMed

    Tanaka, Junichi; Moriyama, Hiroshi; Terada, Masaki; Takada, Toshinori; Suzuki, Eiichi; Narita, Ichiei; Kawabata, Yoshinori; Yamaguchi, Tetsuo; Hebisawa, Akira; Sakai, Fumikazu; Arakawa, Hiroaki

    2014-03-27

    Hard metal lung disease has various pathological patterns including giant cell interstitial pneumonia (GIP) and usual interstitial pneumonia (UIP). Although the UIP pattern is considered the prominent feature in advanced disease, it is unknown whether GIP finally progresses to the UIP pattern. To clarify clinical, pathological and elemental differences between the GIP and UIP patterns in hard metal lung disease. A cross-sectional study of patients from 17 institutes participating in the 10th annual meeting of the Tokyo Research Group for Diffuse Parenchymal Lung Diseases, 2009. Nineteen patients (seven female) diagnosed with hard metal lung disease by the presence of tungsten in lung specimens were studied. Fourteen cases were pathologically diagnosed as GIP or centrilobular inflammation/fibrosing. The other five cases were the UIP pattern or upper lobe fibrosis. Elemental analyses of lung specimens of GIP showed tungsten throughout the centrilobular fibrotic areas. In the UIP pattern, tungsten was detected in the periarteriolar area with subpleural fibrosis, but no association with centrilobular fibrosis or inflammatory cell infiltration. The GIP group was younger (43.1 vs 58.6 years), with shorter exposure duration (73 vs 285 months; p<0.01), lower serum KL-6 (398 vs 710 U/mL) and higher lymphocyte percentage in bronchoalveolar lavage fluid (31.5% vs 3.22%; p<0.05) than the fibrosis group. The UIP pattern or upper lobe fibrosis is remarkably different from GIP in distribution of hard metal elements, associated interstitial inflammation and fibrosis, and clinical features. In hard metal lung disease, the UIP pattern or upper lobe fibrosis may not be an advanced form of GIP.

  15. An observational study of giant cell interstitial pneumonia and lung fibrosis in hard metal lung disease

    PubMed Central

    Tanaka, Junichi; Moriyama, Hiroshi; Terada, Masaki; Takada, Toshinori; Suzuki, Eiichi; Narita, Ichiei; Kawabata, Yoshinori; Yamaguchi, Tetsuo; Hebisawa, Akira; Sakai, Fumikazu; Arakawa, Hiroaki

    2014-01-01

    Background Hard metal lung disease has various pathological patterns including giant cell interstitial pneumonia (GIP) and usual interstitial pneumonia (UIP). Although the UIP pattern is considered the prominent feature in advanced disease, it is unknown whether GIP finally progresses to the UIP pattern. Objectives To clarify clinical, pathological and elemental differences between the GIP and UIP patterns in hard metal lung disease. Methods A cross-sectional study of patients from 17 institutes participating in the 10th annual meeting of the Tokyo Research Group for Diffuse Parenchymal Lung Diseases, 2009. Nineteen patients (seven female) diagnosed with hard metal lung disease by the presence of tungsten in lung specimens were studied. Results Fourteen cases were pathologically diagnosed as GIP or centrilobular inflammation/fibrosing. The other five cases were the UIP pattern or upper lobe fibrosis. Elemental analyses of lung specimens of GIP showed tungsten throughout the centrilobular fibrotic areas. In the UIP pattern, tungsten was detected in the periarteriolar area with subpleural fibrosis, but no association with centrilobular fibrosis or inflammatory cell infiltration. The GIP group was younger (43.1 vs 58.6 years), with shorter exposure duration (73 vs 285 months; p<0.01), lower serum KL-6 (398 vs 710 U/mL) and higher lymphocyte percentage in bronchoalveolar lavage fluid (31.5% vs 3.22%; p<0.05) than the fibrosis group. Conclusions The UIP pattern or upper lobe fibrosis is remarkably different from GIP in distribution of hard metal elements, associated interstitial inflammation and fibrosis, and clinical features. In hard metal lung disease, the UIP pattern or upper lobe fibrosis may not be an advanced form of GIP. PMID:24674995

  16. Somatic POLE mutations cause an ultramutated giant cell high-grade glioma subtype with better prognosis

    PubMed Central

    Erson-Omay, E. Zeynep; Çağlayan, Ahmet Okay; Schultz, Nikolaus; Weinhold, Nils; Omay, S. Bülent; Özduman, Koray; Köksal, Yavuz; Li, Jie; Serin Harmancı, Akdes; Clark, Victoria; Carrión-Grant, Geneive; Baranoski, Jacob; Çağlar, Caner; Barak, Tanyeri; Coşkun, Süleyman; Baran, Burçin; Köse, Doğan; Sun, Jia; Bakırcıoğlu, Mehmet; Moliterno Günel, Jennifer; Pamir, M. Necmettin; Mishra-Gorur, Ketu; Bilguvar, Kaya; Yasuno, Katsuhito; Vortmeyer, Alexander; Huttner, Anita J.; Sander, Chris; Günel, Murat

    2015-01-01

    Background Malignant high-grade gliomas (HGGs), including the most aggressive form, glioblastoma multiforme, show significant clinical and genomic heterogeneity. Despite recent advances, the overall survival of HGGs and their response to treatment remain poor. In order to gain further insight into disease pathophysiology by correlating genomic landscape with clinical behavior, thereby identifying distinct HGG molecular subgroups associated with improved prognosis, we performed a comprehensive genomic analysis. Methods We analyzed and compared 720 exome-sequenced gliomas (136 from Yale, 584 from The Cancer Genome Atlas) based on their genomic, histological, and clinical features. Results We identified a subgroup of HGGs (6 total, 4 adults and 2 children) that harbored a statistically significantly increased number of somatic mutations (mean = 9257.3 vs 76.2, P = .002). All of these “ultramutated” tumors harbored somatic mutations in the exonuclease domain of the polymerase epsilon gene (POLE), displaying a distinctive genetic profile, characterized by genomic stability and increased C-to-A transversions. Histologically, they all harbored multinucleated giant or bizarre cells, some with predominant infiltrating immune cells. One adult and both pediatric patients carried homozygous germline mutations in the mutS homolog 6 (MSH6) gene. In adults, POLE mutations were observed in patients younger than 40 years and were associated with a longer progression-free survival. Conclusions We identified a genomically, histologically, and clinically distinct subgroup of HGGs that harbored somatic POLE mutations and carried an improved prognosis. Identification of distinctive molecular and pathological HGG phenotypes has implications not only for improved classification but also for potential targeted treatments. PMID:25740784

  17. Subependymal giant cell astrocytoma in a genetically negative tuberous sclerosis complex adult: Case report.

    PubMed

    Konakondla, Sanjay; Jayarao, Mayur; Skrade, Jami; Giannini, Caterina; Workman, Michael J; Morgan, Chad J

    2016-11-01

    The well-described entity of Subependymal Giant Cell Astrocytoma (SEGA) in the setting of Tuberous Sclerosis Complex (TSC) is profound in current literature. It has been described in children as well as adults with or without identifiable clinical presentations of tuberous sclerosis. To our knowledge there has not been any report of a negative genetic workup of Tuberous Sclerosis Complex in an adult patient presenting with an isolated SEGA. We present a case of a 25-year-old female with no medical history who presented to the emergency room for headaches. Further workup included gadolinium enhanced MRI of the brain which revealed a homogenously enhancing mass in the left lateral ventricle with eccentric calcification and resultant obstructive hydrocephalus. A left frontal craniotomy with an interhemispheric transcallosal approach was taken for complete removal of the mass. Final pathological diagnosis was SEGA with suggestive cell population, positive GFAP and positive synaptophysin. Genetic testing included TSC1 (MLPA, DNA Sequencing) and TSC2 (MLPA, DNA Sequencing), which were all negative. The panel did not identify mutations associated with Tuberous Sclerosis. Rare cases of isolated SEGA have been reported in patients who do not have typical features of tuberous sclerosis, and may represent minimal penetrance of the disease with an attenuated phenotype. Negative genetic testing, as demonstrated, can be seen in adults with isolated SEGA. With a negative genetic workup of TSC, regular follow up may still be necessary; however this may prove to be low yield for identifying any TSC features in the future. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. GIANT CONVECTION CELL TURNOVER AS AN EXPLANATION OF THE LONG SECONDARY PERIODS IN SEMIREGULAR RED VARIABLE STARS

    SciTech Connect

    Stothers, Richard B.

    2010-12-10

    Giant convection cells in the envelopes of massive red supergiants turn over in a time comparable in order of magnitude with the observed long secondary periods in these stars, according to a theory proposed some years ago by Stothers and Leung. This idea is developed further here by using improved theoretical data, especially a more accurate convective mixing length and a simple calculation of the expected radial-velocity variations at the stellar surface. The theory is applied to the two best-observed red supergiants, Betelgeuse and Antares, with more success than in the earlier study. The theory can also explain the long secondary periods seen in the low-mass red giants, thus providing a uniform and coherent picture for all of the semiregular red variables. How the turnover of a giant convection cell might account for the observed slow light and radial-velocity variations, their relative phasing, and the absence of these variations in certain stars is discussed here in a qualitative way, but follows naturally from the theory.

  19. Successful Treatment of Giant Basal Cell Carcinoma with Topical Imiquimod 5% Cream with Long Term Follow-up

    PubMed Central

    Chun-Guang, M; Qi-Man, L; Yu-Yun, ZH; Li-Hua, CH; Cheng, Tiffany; Jian-De, H

    2014-01-01

    The use of the topical Imiquimod 5% cream offers a noninvasive, nonsurgical, and an effective option for the treatment of primary small (<2 cm) superficial basal cell carcinoma (sBCC). However, reports about successful treatment of giant (>5 cm) BCC with topical Imiquimod 5% cream are rare. We present our experience in the treatment of two giant tumors (6 × 8 cm2, 5.2 × 4.2 cm2) of BCC on the face with Imiquimod 5% cream, 2 to 3 days/week for 12 weeks. Both the tumors were cured with clinical and pathological evidence, one with 6-year follow-up and the other with 3.5-year follow-up. PMID:25484387

  20. Successful Treatment of Giant Basal Cell Carcinoma with Topical Imiquimod 5% Cream with Long Term Follow-up.

    PubMed

    Chun-Guang, M; Qi-Man, L; Yu-Yun, Zh; Li-Hua, Ch; Cheng, Tiffany; Jian-De, H

    2014-11-01

    The use of the topical Imiquimod 5% cream offers a noninvasive, nonsurgical, and an effective option for the treatment of primary small (<2 cm) superficial basal cell carcinoma (sBCC). However, reports about successful treatment of giant (>5 cm) BCC with topical Imiquimod 5% cream are rare. We present our experience in the treatment of two giant tumors (6 × 8 cm(2), 5.2 × 4.2 cm(2)) of BCC on the face with Imiquimod 5% cream, 2 to 3 days/week for 12 weeks. Both the tumors were cured with clinical and pathological evidence, one with 6-year follow-up and the other with 3.5-year follow-up.

  1. Cellular localization of metabotropic glutamate receptors in cortical tubers and subependymal giant cell tumors of tuberous sclerosis complex.

    PubMed

    Boer, K; Troost, D; Timmermans, W; Gorter, J A; Spliet, W G M; Nellist, M; Jansen, F; Aronica, E

    2008-09-22

    Tuberous sclerosis complex (TSC) is an autosomal dominant disorder associated with cortical malformations (cortical tubers) and the development of glial tumors (subependymal giant-cell tumors, SGCTs). Expression of metabotropic glutamate receptor (mGluR) subtypes is developmentally regulated and several studies suggest an involvement of mGluR-mediated glutamate signaling in the regulation of proliferation and survival of neural stem-progenitor cells, as well as in the control of tumor growth. In the present study, we have investigated the expression and cell-specific distribution of group I (mGluR1, mGluR5), group II (mGluR2/3) and group III (mGluR4 and mGluR8) mGluR subtypes in human TSC specimens of both cortical tubers and SGCTs, using immunocytochemistry. Strong group I mGluR immunoreactivity (IR) was observed in the large majority of TSC specimens in dysplastic neurons and in giant cells within cortical tubers, as well as in tumor cells within SGCTs. In particular mGluR5 appeared to be most frequently expressed, whereas mGluR1alpha was detected in a subpopulation of neurons and giant cells. Cells expressing mGluR1alpha and mGluR5, demonstrate IR for phospho-S6 ribosomal protein (PS6), which is a marker of the mammalian target of rapamycin (mTOR) pathway activation. Group II and particularly group III mGluR IR was less frequently observed than group I mGluRs in dysplastic neurons and giant cells of tubers and tumor cells of SGCTs. Reactive astrocytes were mainly stained with mGluR5 and mGluR2/3. These findings expand our knowledge concerning the cellular phenotype in cortical tubers and in SGCTs and highlight the role of group I mGluRs as important mediators of glutamate signaling in TSC brain lesions. Individual mGluR subtypes may represent potential pharmacological targets for the treatment of the neurological manifestations associated with TSC brain lesions.

  2. Sustained long-term complete regression of a giant cell tumor of the spine after treatment with denosumab.

    PubMed

    Mattei, Tobias A; Ramos, Edwin; Rehman, Azeem A; Shaw, Andrew; Patel, Shreyasumar R; Mendel, Ehud

    2014-07-01

    Although giant cell tumors (GCTs) are histologically benign, they may become locally aggressive bone tumors. As these lesions tend to respond poorly to radio- and chemotherapy, currently the standard surgical paradigm for the treatment of spinal GCTs involves en bloc surgical resection. Denosumab is a newly developed monoclonal antibody designed to inhibit the receptor activator of nuclear factor kappa-B ligand (RANKL) which has already been demonstrated to induce marked radiographic responses on GCTs of the appendicular skeleton. Nevertheless, the role of denosumab in the treatment algorithm of GCTs of the spine has not yet been defined. To describe the first case of sustained long-term complete clinical and radiographic regression of a GCT of the spine after treatment with the new RANKL antibody denosumab. Case report and literature review. The authors describe the case of 22-year-old female patient, harboring a GCT involving the C2 vertebral body and odontoid process, who was treated in monotherapy with denosumab, resulting in complete long-term clinical and radiographic tumor remission. There were no major side effects associated with the long-term pharmacological treatment with denosumab. From the clinical standpoint, the patient demonstrated complete remission of the disease while under treatment. The 16-month radiographic follow-up demonstrated complete disappearance of the osteolytic process and intense new cortical bone formation with restoration of the bone integrity of the C2 vertebral body. This is the first report of sustained long-term complete clinical and radiographic regression of a GCT of the spine after treatment with the new RANKL antibody denosumab. Although future long-term follow-up studies are still necessary to establish important key points regarding the best therapeutic protoco