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

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.

Giant cell bone lesions in the craniofacial region: a diagnostic and therapeutic challenge

Background: Giant cell tumors of bone (GCTs) are common in the long bones, but rare in the craniofacial region, with only 1% of cases occurring in the latter. Clinical, radiological, and anatomical diagnosis of this locally aggressive disease, which occurs in response to trauma or neoplastic transformation, poses a major challenge in clinical practice. Methods: The present study describes a series of 4 cases and highlights the main features of the differential diagnosis and treatment of these lesions: GCT, giant cell reparative granuloma (GCRG), and the brown tumor of hyperparathyroidism. Results: GCT presents as a benign neoplasm, most typically affecting the knees, and rarely in the temporal and sphenoid bones. It is radiologically indistinguishable from GCRG due to its lytic, poorly defined appearance. The distinction can only be made microscopically, as the presence of multinucleated giant cells scattered throughout the stroma and the absence of a history of trauma favor a diagnosis of GCT. The brown tumor of hyperparathyroidism occurs with rapid, localized osteoclast activity secondary to the effects of increased parathyroid hormone (PTH) levels; parathyroid examination is indispensable. Conclusion: The diagnosis and treatment of these lesions poses a major challenge due to their similar clinical presentation and radiological appearance. Accurate diagnosis is essential for definition of appropriate management, as complete resection is the goal in GCT and GCRG to avoid recurrence, whereas the brown tumor often yields to treatment of the underlying hyperparathyroidism.

Intralesional corticosteroid injections in the treatment of central giant cell lesions of the jaws

Objective: The aim of this study was to evaluate the response of treatment of central giant cell lesion to intralesional corticosteroid injections. Study Design: Review of articles indexed in PubMed on the topic between the years 1988 and 2011, and development of a descriptive meta-analysis of the results. Results: Sample of 41 patients primarily treated with intralesional corticosteroid injections was obtained, with a male female ratio of 1:0.95, being 23 aggressive and 18 non-aggressive central giant cell lesions. Triamcinolone acetonide and triamcinolone hexacetonide were the drugs used, and 78.0% cases were considered as good result, 14.6% were considered as moderate response and 7.3% were considered as negative result to treatment. Considering the aggressiveness, 88.9% of non-aggressive lesions presented a good response to treatment, in aggressive central giant cell lesions, 69.6% presented a good response to intralesional corticosteroid injections. Conclusion: In view of the results analyzed, intralesional corticosteroid injections could be considered as first treatment option for central giant cell lesion.

Central giant cell granuloma

Background: Central giant cell granuloma is a benign condition of the jaws which may present an aggressive behavior. Case report: A 9-year-old boy was complaining of swelling in the floor of the mouth. A solid swelling was observed in the area of the lower incisors. From the radiographic exam, we observed a radiolucent image in the mandibular bone with well-defined limits extending from the apical region of tooth 33 to the apical region of tooth 42. Discussion: Due to the diagnosis and the age of the patient, we chose a conservative treatment, administering subcutaneous injections of calcitonin. During this treatment, no reduction to the lesion was observed. Therefore, we chose to treat the lesion with triamcinolone acetonide. Monthly follow-ups demonstrated good lesion reduction and the absence of any clinical symptoms during the first 2 years. After a 3-year follow-up, the patient returned, presenting mobility of the lower incisors. A significant increase in the size of the lesion was observed. After a biopsy, with the removal of tissuewhich had the appearance of a cyst capsule, microscopic analyses were found to be compatible with a secondarily infected cyst. Two months following this procedure, the patient did not present tooth mobility anymore and the oral mucosa presented a normal aspect. Following a radiographic exam, full lesion repair was observed. These conservative treatments should be the first option in cases of central giant cell granuloma and the patient must be observed for a long period of time, until no further clinical or radiographic signs of lesions are observed

Expression of NADPH Oxidase by Trophoblast Cells: Potential Implications for the Postimplanting Mouse Embryo

Cytochemical localization of hydrogen peroxide-generating sites suggests NADPH (nicotinamide adenine dinucleotide 3-phosphate [ reduced form]) oxidase expression at the maternal-fetal interface. To explore this possibility, we have characterized the expression and activity of the NADPH oxidase complex in trophoblast cells during the postimplantation period. Implantation sites and ectoplacental cones (EPCs) from 7.5-gestational day embryos from CD1 mice were used as a source for expression analyses of NADPH oxidase catalytic and regulatory subunits. EPCs grown in primary culture were used to investigate the production of superoxide anion through dihydroxyethidium oxidation in confocal microscopy and immunohistochemical assays. NADPH subunits Cybb (gp91phox), Cyba (p22phox), Ncf4 (p40phox), Ncf1 (p47phox), Ncf2 (p67phox), and Rac1 were expressed by trophoblast cells. The fundamental subunits of membrane CYBB and cytosolic NCF2 were markedly upregulated after phorbol-12-myristate-13-acetate (PMA) treatment, as detected by quantitative real-time PCR, Western blotting, and immunohistochemistry. Fluorescence microscopy imaging showed colocalization of cytosolic and plasma membrane NADPH oxidase subunits mainly after PMA treatment, suggesting assembly of the complex after enzyme activation. Cultured EPCs produced superoxide in a NADPH-dependent manner, associating the NADPH oxidase-mediated superoxide production with postimplantation trophoblast physiology. NADPH-oxidase cDNA subunit sequencing showed a high degree of homology between the trophoblast and neutrophil isoforms of the oxidase, emphasizing a putative role for reactive oxygen species production in phagocytic activity and innate immune responses.

Interferon-gamma alters the phagocytic activity of the mouse trophoblast

Interferon-gamma (IFN-gamma) mediates diverse functions in bone marrow-derived phagocytes, including phagocytosis and microbe destruction. This cytokine has also been detected at implantation sites under both physiological and pathological conditions in many different species. At these particular sites, the outermost embryonic cell layer in close contact with the maternal tissues, the trophoblast exhibits intense phagocytic activity. To determine whether IFN-gamma affects phagocytosis of mouse-trophoblast cells, ectoplacental cone-derived trophoblast was cultured and evaluated for erythrophagocytosis. Phagocytic activity was monitored ultrastructurally and expressed as percentage of phagocytic trophoblast in total trophoblast cells. Conditioned medium from concanavalin-A-stimulated spleen cells significantly enhanced trophoblast phagocytosis. This effect was blocked by pre-incubation with an anti-IFN-gamma neutralizing antibody. Introduction of mouse recombinant IFN-gamma (mrIFN-gamma) to cultures did not increase cell death, but augmented the percentage of phagocytic cells in a dose-dependent manner. Ectoplacental cones from mice deficient for IFN-gamma receptor alpha-chain showed a significant decrease of the phagocytosis, even under mrIFN-gamma stimulation, suggesting that IFN-gamma-induced phagocytosis are receptor-mediated. Reverse transcriptase-PCR analyses confirmed the presence of mRNA for IFN-gamma receptor alpha and beta-chains in trophoblast cells and detected a significant increase in the mRNA levels of IFN-gamma receptor beta-chain, mainly, when cultured cells were exposed to IFN-gamma. Immunohistochemistry and Western blot analyses also revealed protein expression of the IFN-gamma receptor alpha-chain. These results suggest that IFN-gamma may participate in the phagocytic activation of the mouse trophoblast, albeit the exact mechanism was not hereby elucidated. Protective and/or nutritional fetal benefit may result from this physiological response. In addition, our data also shed some light on the understanding of trophoblast tolerance to inflammatory/immune cytokines during normal gestation.

Patterns of cell proliferation and apoptosis by topographic region in normal Bos taurus vs. Bos indicus crossbreeds bovine placentae during pregnancy

Background: Placental and fetal growth requires high rates of cellular turnover and differentiation, which contributes to conceptus development. The trophoblast has unique properties and a wide range of metabolic, endocrine and angiogenic functions, but the proliferative profile of the bovine placenta characterized by flow cytometry analysis and its role in fetal development are currently uncharacterized. Complete understanding of placental apoptotic and proliferative rates may be relevant to development, especially if related to the pathogenesis of pregnancy losses and placental abnormalities. Methods: In this study, the proliferation activity and apoptosis in different regions of normal bovine placenta (central and boundary regions of placentomes, placentomal fusion, microplacentomes, and interplacentomal regions), from distinct gestation periods (Days 70 to 290 of pregnancy), were analyzed by flow cytometry. Results: Our results indicated that microplacentomes presented a lower number of apoptotic cells throughout pregnancy, with a higher proliferative activity by the end of gestation, suggesting that such structures do not contribute significantly to normal of placental functions and conceptus development during pregnancy. The placentome edges revealed a higher number of apoptotic cells from Day 170 on, which suggests that placentome detachment may well initiate in this region. Conclusion: Variations involving proliferation and apoptotic rates may influence placental maturation and detachment, compromising placental functions and leading to fetal stress, abnormalities in development and abortion, as frequently seen in bovine pregnancies from in vitro fertilization and cloning procedures. Our findings describing the pattern of cell proliferation and apoptosis in normal bovine pregnancies may be useful for unraveling some of the developmental deviations seen in nature and after in vitro embryo manipulations.