Assuntos
Granuloma de Células Gigantes , Doenças Mandibulares , Humanos , Granuloma de Células Gigantes/diagnóstico por imagem , Granuloma de Células Gigantes/patologia , Doenças Mandibulares/diagnóstico por imagem , Doenças Mandibulares/patologia , Diagnóstico Diferencial , Masculino , Tomografia Computadorizada por Raios X/métodos , Criança , Feminino , Radiografia PanorâmicaRESUMO
Sporadic giant cell granulomas (GCGs) of the jaws and cherubism-associated giant cell lesions share histopathological features and microscopic diagnosis alone can be challenging. Additionally, GCG can morphologically closely resemble other giant cell-rich lesions, including non-ossifying fibroma (NOF), aneurysmal bone cyst (ABC), giant cell tumour of bone (GCTB), and chondroblastoma. The epigenetic basis of these giant cell-rich tumours is unclear and DNA methylation profiling has been shown to be clinically useful for the diagnosis of other tumour types. Therefore, we aimed to assess the DNA methylation profile of central and peripheral sporadic GCG and cherubism to test whether DNA methylation patterns can help to distinguish them. Additionally, we compared the DNA methylation profile of these lesions with those of other giant cell-rich mimics to investigate if the microscopic similarities extend to the epigenetic level. DNA methylation analysis was performed for central (n = 10) and peripheral (n = 10) GCG, cherubism (n = 6), NOF (n = 10), ABC (n = 16), GCTB (n = 9), and chondroblastoma (n = 10) using the Infinium Human Methylation EPIC Chip. Central and peripheral sporadic GCG and cherubism share a related DNA methylation pattern, with those of peripheral GCG and cherubism appearing slightly distinct, while central GCG shows overlap with both of the former. NOF, ABC, GCTB, and chondroblastoma, on the other hand, have distinct methylation patterns. The global and enhancer-associated CpG DNA methylation values showed a similar distribution pattern among central and peripheral GCG and cherubism, with cherubism showing the lowest and peripheral GCG having the highest median values. By contrast, promoter regions showed a different methylation distribution pattern, with cherubism showing the highest median values. In conclusion, DNA methylation profiling is currently not capable of clearly distinguishing sporadic and cherubism-associated giant cell lesions. Conversely, it could discriminate sporadic GCG of the jaws from their giant cell-rich mimics (NOF, ABC, GCTB, and chondroblastoma).
Assuntos
Neoplasias Ósseas , Querubismo , Condroblastoma , Tumor de Células Gigantes do Osso , Granuloma de Células Gigantes , Humanos , Querubismo/diagnóstico , Querubismo/genética , Querubismo/patologia , Granuloma de Células Gigantes/diagnóstico , Granuloma de Células Gigantes/genética , Granuloma de Células Gigantes/patologia , Condroblastoma/diagnóstico , Condroblastoma/genética , Condroblastoma/patologia , Metilação de DNA , Células Gigantes/patologia , Tumor de Células Gigantes do Osso/diagnóstico , Tumor de Células Gigantes do Osso/genética , Tumor de Células Gigantes do Osso/patologia , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Arcada Osseodentária/patologiaRESUMO
Annular elastolytic giant cell granuloma is an uncommon granulomatous cutaneous disease that usually affects sun-exposed skin. Non-scarring alopecia is a possible presentation. Although histopathology is mandatory for the diagnosis, dermoscopy may help to narrow down the clinical differential diagnosis. The authors report a case of annular elastolytic giant cell granuloma in the scalp of a female adult patient, showing multiple yellowish/orange follicular dots in a diffuse erythemato-whitish background in the dermoscopy.
Assuntos
Granuloma Anular , Granuloma de Células Gigantes , Dermatopatias , Adulto , Dermoscopia , Feminino , Granuloma Anular/patologia , Granuloma de Células Gigantes/diagnóstico por imagem , Granuloma de Células Gigantes/patologia , Humanos , Pele/patologia , Dermatopatias/diagnóstico por imagem , Dermatopatias/patologiaRESUMO
INTRODUCTION: Central Giant Cell Granuloma is an infrequent bone lesion located mainly in the maxillary bone. The main treatment is surgery with wide margins, so it sometimes causes great morbidity and esthetic al terations. Denosumab, a RANK-ligand inhibitor monoclonal antibody, has been presented as a valid therapeutic alternative in the treatment of these lesions. OBJECTIVE: to describe the clinical and radio logical response after treatment with Denosumab in a patient with unresected giant cell granuloma. CLINICAL CASE: 12-year-old boy who consulted due to a 24-hour maxillary swelling, without other associated symptoms. Examination revealed a tumor in the upper left maxilla with bulging of the ip- silateral gingiva. A CT scan was performed which showed a large expansive intraosseous lesion in the maxillary alveolar ridge. The biopsy of the lesion was compatible with Central Giant Cell Granuloma. Due to the size and location of the lesion, initial treatment with Denosumab, a human monoclonal antibody with action on RANK-ligand, was indicated. After 10 months of treatment, the patient showed a favorable clinical and radiological response, with a size decrease of the lesion and metabolic activity. As an adverse effect, the boy presented mild hypocalcemia, resolved after supplementation with calcium. CONCLUSION: the use of Denosumab as the first line of treatment in Giant Cell Granu loma may be an adequate therapeutic option in adolescents with lesions that are difficult to resect.
Assuntos
Granuloma de Células Gigantes , Adolescente , Criança , Denosumab/uso terapêutico , Granuloma de Células Gigantes/diagnóstico por imagem , Granuloma de Células Gigantes/tratamento farmacológico , Granuloma de Células Gigantes/patologia , Humanos , Ligantes , Masculino , Ligante RANK/uso terapêutico , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: This study seeks to investigate immunohistochemical parameters that could distinguish non-aggressive Central giant cell granuloma (CGCG) from aggressive CGCG, two groups of lesions which differ in their clinical and radiographic features and prognosis. MATERIAL AND METHODS: 12 cases of non-aggressive CGCG and 11 cases of aggressive CGCG were investigated and associated the immunohistochemical expression of macrophages (CD68 and CD163), blood vessels (CD34 and CD105), lymphatic vessels (D2-40) and regulator proteins (p63 and Ki-67). Clinical and radiographic features were also studied. RESULTS: Associations between all proteins in non-aggressive and aggressive CGCG were not significant (p > 0.05). With respect to non-aggressive CGCG, there were no significant correlations, while in aggressive CGCG there was a significant positive correlation between CD68 and CD163 (p = 0.031), between CD34 and D2-40 proteins (p = 0.04), whereas a significant negative correlation was observed between CD105 and CD68 (p = 0.040). However, regardless of aggressiveness of CGCG, there was a significant positive correlation between CD68 and CD163 (p = 0,04). Among the clinical and immunohistochemical aspects, only the symptomatology was a significant risk factor for the occurrence of aggressive CGCG (OR = 12.00/p = 0.016). CONCLUSION: Macrophages and angiogenesis contribute to their maintenance and development of CGCG. In addition, immunohistochemistry used here was not able to differentiate their aggressiveness. However, symptomatology was proved to be a risk factor for the occurrence of aggressive CGCG. It is possible that clinical features, particularly symptomatology, represent the most appropriate parameter to attempt to distinguish GCCG.
Assuntos
Granuloma de Células Gigantes/patologia , Doenças Maxilomandibulares/patologia , Macrófagos/patologia , Neovascularização Patológica/patologia , Adulto , Biomarcadores/análise , Vasos Sanguíneos/patologia , Feminino , Granuloma de Células Gigantes/metabolismo , Humanos , Imuno-Histoquímica , Vasos Linfáticos/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Central giant cell granuloma (CGCG) is a benign intraosseous lesion of the head and neck with potential for aggressive and locally destructive behaviour. Lesions of the maxilla tend to expand more than those of the mandible due to the thinner cortices and spongy tissue of this location. Surgical removal is the most common treatment; however, it may be disfiguring in aggressive cases, especially for lesions located in the maxilla. Alternative treatments, such as intralesional corticosteroid injections, have been performed with satisfactory results. We report a case of a 12-year-old female patient with a CGCG of the left maxilla that was treated with 40 doses of intralesional triamcinolone acetonide infiltrations combined with alendronate sodium and calcium carbonate. Clinical and imaging follow-up over 12 years demonstrates improvement in the patient's condition.
Assuntos
Corticosteroides/administração & dosagem , Difosfonatos/administração & dosagem , Granuloma de Células Gigantes/tratamento farmacológico , Granuloma de Células Gigantes/patologia , Doenças Maxilares/tratamento farmacológico , Doenças Maxilares/patologia , Alendronato/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Conservadores da Densidade Óssea/administração & dosagem , Carbonato de Cálcio/administração & dosagem , Criança , Feminino , Seguimentos , Humanos , Injeções Intralesionais , Tempo , Triancinolona Acetonida/administração & dosagemRESUMO
Next-generation sequencing has revealed mutations in several bone-related lesions and was recently used to uncover the genetic basis of giant cell lesions of the jaws (GCLJ). Consistent with their benign nature, GCLJ show a low tumor mutation burden. They also harbor somatic, heterozygous, mutually exclusive mutations in TRPV4, KRAS, or FGFR1. These signature mutations occur only in a subset of lesional cells, suggesting the existence of a 'landscaping effect', with mutant cells inducing abnormal accumulation of non-mutant cells that form the tumor mass. Osteoclast-rich lesions with histological similarities to GCLJ can occur in the jaws sporadically or in association with genetically inherited syndromes. Based on recent results, the pathogenesis of a subgroup of sporadic GCLJ seems closely related to non-ossifying fibroma of long bones, with both lesions sharing MAPK pathway-activating mutations. In this review, we extrapolate from these recent findings to contextualize GCLJ genetics and we highlight the therapeutic implications of this new information. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Assuntos
Tumores de Células Gigantes/genética , Neoplasias Maxilomandibulares/genética , Tumores de Células Gigantes/patologia , Tumores de Células Gigantes/terapia , Granuloma de Células Gigantes/genética , Granuloma de Células Gigantes/patologia , Granuloma de Células Gigantes/terapia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Neoplasias Maxilomandibulares/patologia , Neoplasias Maxilomandibulares/terapia , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Canais de Cátion TRPV/genéticaRESUMO
RESUMEN: Se presenta el caso de un paciente sexo femenino 31 años, insuficienciente renal crónica en hemodiálisis, hipertensa secundaria, consulta por aumento de volumen oral en relación a encía marginal vestibular izquierda, 6 meses de evolución. Al examen se observa aumento de volumen de 15 mm en relación a piezas. 3.6 y 3.7. Radiografía muestra compromiso periodontal pieza 3.7. Se realiza biopsia excisional y exodoncia pieza 3.7. Histopatología informa granuloma periférico de células gigantes. Se solicitan exámenes de laboratorio para estudio de hiperparatiroidismo (PTH elevada, calcemia fosfatemia normales). Evoluciona favorablemente. Sin signos de recidiva a los 3 meses. El diagnóstico histopatológico de lesión de células gigantes debe ser complementado con la clínica, exámenes de laboratorio e imagenología, el objetivo final es definir si tal diagnóstico corresponde a un tumor pardo, a un granuloma central de células gigantes o a un granuloma periférico de células gigantes. En la literatura los reportes de asociación entre granuloma periférico de células gigantes e hiperparatiroidismo son escasos. Este caso corresponde a granuloma periférico células gigantes, asociado a hipersecreción de paratohormona.
ABSTRACT: A 31-year-old female patient with chronic renal insufficiency in hemodialysis and secondary hypertension consulted due to an enlarging intraoral lesion in relation to the left marginal vestibular gingival, with 6 months of evolution. A 15mm mass in relation to mandibular left molars was noted. Radiograph showed periodontal involvement of mandibular left second molar. Excisional biopsy and tooth 3.7 extraction were performed. Histopathology reported a peripheral giant cell granuloma. Laboratory tests were requested for suspected hyperparathyroidism (aiding in the diagnosis) (high PTH, normal phosphatemia and calcemia). Evolution was favorable, without signs of reappearance after 3 months. The histopathological diagnosis of giant cell lesions should be complemented with clinical, laboratory and imaging tests. The final objective is to make the differential diagnosis between brown tumor, central giant cell granuloma and peripheral giant cell granuloma because the treatment varies considerably. There are few reports in the literature about the association between peripheral giant cell granuloma and hyperparathyroidism. This case corresponds to peripheral giant cell granuloma, possibly associated with parathormone hypersecretion.
Assuntos
Humanos , Feminino , Adulto , Neoplasias das Paratireoides/cirurgia , Granuloma de Células Gigantes/diagnóstico , Granuloma de Células Gigantes/patologia , Hiperparatireoidismo Primário/cirurgia , Doenças da Gengiva/etiologia , Doenças da Gengiva/patologia , Radiografia Panorâmica , Procedimentos Cirúrgicos Bucais/métodos , Doenças da Gengiva/cirurgiaRESUMO
Abstract Introduction: Oral peripheral and central giant cell granulomas are lesions with little-known etiology and pathogenesis. Objective: The aim of this study was to compare matrix metalloproteinases-2 and osteopontin protein expression in the multinucleated giant cells and mononuclear cells of the peripheral and central giant cell granuloma lesions. Methods: In this retrospective study, the presence of matrix metalloproteinases-2 and osteopontin in 37 cases of central giant cell granuloma and 37 cases of peripheral giant cell granuloma paraffin blocks were assessed by streptavidin-biotin immunohistochemistry. Independent sample t-test, Chi-square, Mann-Whitney tests and Spearman's rank correlation coefficient were used. Results: The osteopontin was expressed in both multinucleated giant cells and mononuclear cells in all cases of peripheral and central giant cells granulomas. However, the matrix metalloproteinases-2 expression was positive in 86.5% of giant cells and it was positive in all of mononuclear cells in peripheral giant cells granuloma. In central giant cells granulomas, 91.8% of giant cells and all mononuclear cells were positive for matrix metalloproteinases-2 marker. Percentage and Intensity of staining were significantly higher in central than peripheral giant cells lesions, for both markers (p ˂ 0.05). Conclusion: This study showed that the expression of osteopontin in giant cells supports the theory of osteolcastic nature of these cells. Also, the presence of osteopontin and matrix metalloproteinases-2 in mononuclear cells may indicate the monocyte-macrophage origin of these cells, as the differentiation of the precursors of the mononuclear stromal monocyte/macrophage to osteoclasts is possibly affected by the expression of osteolytic factors. Also, may be differences in biological behaviors of these lesions are associated with the level of osteopontin and matrix metalloproteinases-2 expression.
Resumo Introdução: Os granulomas periféricos e centrais de células gigantes são lesões com etiologia e patogênese pouco conhecidas. Objetivo: Comparar a expressão das proteínas metaloproteinases da matriz-2 e osteopontina nas células gigantes multinucleadas e células mononucleares no granuloma periférico e central de células gigantes. Método: Neste estudo retrospectivo, a presença de metaloproteinases da matriz-2 e osteopontina em 37 casos de granuloma central de células gigantes e 37 casos de granuloma periférico de células gigantes em blocos de parafina foi avaliada por imuno-histoquímica pela estreptavidina-biotina. Foram usados teste t para amostra independente, teste de qui-quadrado, Mann-Whitney e coeficiente de correlação de Spearman. Resultados: A osteopontina foi expressa em células gigantes multinucleadas e células mononucleares em todos os casos de granuloma periférico de células gigantes e granuloma central de células gigantes. No entanto, a expressão de metaloproteinases da matriz-2 foi positiva em 86,5% de células gigantes e foi positiva em todas as células mononucleares em granuloma periférico de células gigantes. Em granuloma central de células gigantes, 91,8% das células gigantes e todas as células mononucleares foram positivas para o marcador metaloproteinases da matriz-2. A porcentagem e intensidade de coloração em granuloma central de células gigantes foram significantemente maiores do que em granuloma periférico de células gigantes para ambos os marcadores (p ˂ 0,05). Conclusão: Este estudo mostrou que a expressão de osteopontina em células gigantes apoia a teoria da natureza osteoclástica dessas células. Além disso, a presença de osteopontina e metaloproteinases da matriz-2 em células mononucleares pode indicar a origem dos monócitos-macrófagos dessas células, uma vez que a diferenciação dos precursores do monócito/macrófago estromal mononuclear em osteoclastos é possivelmente afetada pela expressão de fatores osteolíticos. Além disso, as diferenças nos comportamentos biológicos dessas lesões estão associadas ao nível de expressão de osteopontina e metaloproteinases da matriz-2.