ABSTRACT
BACKGROUND: Cherubism is a rare autosomal dominant disorder of the jaws caused by mutation of the SH3BP2 gene. The bone is replaced by a fibrous granuloma containing multinucleated giant cells. Cells of the cherubism granuloma have never been systematically analyzed. Hence, the aim of this study was to characterize the cells in human cherubism granulomas, to determine the osteoclastic characteristics of the multinucleated giant cells and to investigate the potential role of TNF-α in human cherubism. RESULTS: Seven granulomas were analyzed in pathology, molecular biology and immunohistochemistry. Granulomas were composed mainly of macrophages or osteoclasts within a fibroblastic tissue, with few lymphoid cells. Myeloid differentiation and nuclear NFATc1 localization were both associated with disease aggressiveness. OPG and RANKL immunohistochemical expression was unexpected in our specimens. Five granuloma cells were cultured in standard and osteoclastogenic media. In culture, cherubism cells were able to differentiate into active osteoclasts, in both osteoclastogenic and standard media. IL-6 was the major cytokine present in the culture supernatants. CONCLUSION: Multinucleated giant cells from cherubism granulomas are CD68 positive cells, which differentiate into macrophages in non-aggressive cherubism and into osteoclasts in aggressive cherubism, stimulated by the NFATc1 pathway. This latter differentiation appears to involve a disturbed RANK-L/RANK/OPG pathway and be less TNF-α dependent than the cherubism mouse model.
Subject(s)
Cherubism/pathology , Osteoclasts/cytology , Osteoclasts/metabolism , Osteogenesis/physiology , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , Adolescent , Adult , Cell Differentiation/genetics , Cell Differentiation/physiology , Cherubism/metabolism , Child , Female , Humans , Immunohistochemistry , Interleukin-6/metabolism , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , Mutation/genetics , NFATC Transcription Factors/genetics , NFATC Transcription Factors/metabolism , Osteogenesis/genetics , Osteoprotegerin/genetics , Osteoprotegerin/metabolism , RANK Ligand/genetics , RANK Ligand/metabolism , Receptors, Tumor Necrosis Factor, Type I/genetics , Receptors, Tumor Necrosis Factor, Type I/metabolism , Tumor Cells, Cultured , Vimentin/genetics , Vimentin/metabolism , Young AdultABSTRACT
A clinical case is presented of a 70-year-old woman suffering from a right hemilingual epidermoid carcinoma. A step-by-step video description of the regional infrahyoid island flap is presented and narrated. Long-term results at 2 months in terms of aesthetics and function at the recipient and donor sites are excellent. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.
Subject(s)
Carcinoma, Squamous Cell/surgery , Mouth Neoplasms/surgery , Myocutaneous Flap , Plastic Surgery Procedures/methods , Aged , Female , Follow-Up Studies , Humans , Time FactorsABSTRACT
Cherubism is a rare genetic disease characterized by bilateral giant cell reparative granuloma of the jaws consisting of a fibrotic stroma with giant multinucleated cells (GMCs) and osteoclastic features. Cherubism severity is highly variable, and recurrence after surgery is the most important risk. Currently, there are no prognostic indicators. The aims of this study were to evaluate the osteoclastogenesis phenotype by histologic examination of nuclear factor of activated T cells 1 (NFATc1) localization and tartrate-resistant acid phosphatase (TRAP) activity and to correlate the results to disease aggressiveness to define prognostic indicators. Based on cherubism evolution 1 year after surgery, 3 classes of cherubism aggressiveness were identified: mild (group A), moderate (group B), and severe (group C). Histologically, in grade A and B cherubism lesions, GMCs were negative for both TRAP activity and NFATc1 nuclear localization. In contrast, in grade C cherubism lesions, GMCs were all positive for TRAP activity and NFATc1 nuclear localization and displayed osteoclast-like features. Other histopathologic findings were not different among the 3 groups. Our results establish that TRAP activity and NFTAc1 nuclear localization are associated with aggressive cherubism and therefore could be added to routine pathologic examination to aid in prognosis and management of the disease. The finding of NFATc1 nuclear localization in aggressive tumors supports the addition of anticalcineurin treatment to the therapeutic arsenal for cherubism.
Subject(s)
Cell Nucleus/chemistry , Cherubism/diagnosis , Giant Cells/chemistry , Jaw/chemistry , NFATC Transcription Factors/analysis , Osteoclasts/chemistry , Adaptor Proteins, Signal Transducing/genetics , Adolescent , Biomarkers/analysis , Cell Nucleus/pathology , Cherubism/metabolism , Cherubism/pathology , Cherubism/surgery , Child , Female , Genetic Predisposition to Disease , Giant Cells/pathology , Humans , Immunohistochemistry , Jaw/pathology , Male , Mutation , Orthognathic Surgical Procedures , Osteoclasts/pathology , Phenotype , Predictive Value of Tests , Prospective Studies , Severity of Illness Index , Tartrate-Resistant Acid Phosphatase/analysis , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Satisfaction with breasts, sexual well-being, psychosocial well-being, and physical well-being are essential outcome factors following breast augmentation surgery in male-to-female transsexual patients. The aim of this study was to measure change in patient satisfaction with breasts and sexual, physical, and psychosocial well-being after breast augmentation in male-to-female transsexual patients. METHODS: All consecutive male-to-female transsexual patients who underwent breast augmentation between 2008 and 2012 were asked to complete the BREAST-Q Augmentation module questionnaire before surgery, at 4 months, and later after surgery. A prospective cohort study was designed and postoperative scores were compared with baseline scores. Satisfaction with breasts and sexual, physical, and psychosocial outcomes assessment was based on the BREAST-Q. RESULTS: Thirty-five male-to-female transsexual patients completed the questionnaires. BREAST-Q subscale median scores (satisfaction with breasts, +59 points; sexual well-being, +34 points; and psychosocial well-being, +48 points) improved significantly (p < 0.05) at 4 months postoperatively and later. No significant change was observed in physical well-being. CONCLUSIONS: In this prospective, noncomparative, cohort study, the current results suggest that the gains in breast satisfaction, psychosocial well-being, and sexual well-being after male-to-female transsexual patients undergo breast augmentation are statistically significant and clinically meaningful to the patient at 4 months after surgery and in the long term. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.