Displasia fibrosa ósea / Fibrous dysplasia of bone

La displasia fibrosa ósea es un trastorno no hereditario del desarrollo esquelético caracterizado por una proliferación anormal de fibroblastos y diferenciación deficiente de osteoblastos que conduce a un reemplazo del tejido óseo esponjoso por tejido conectivo fibroso. Es producida por una mutación somática activadora del gen GNAS1 que induce una activación y proliferación de células mesenquimales indiferenciadas con formación de tejido fibroso y trabéculas óseas anómalas. Existen formas monostóticas, poliostóticas y craneofaciales con diversos grados de dolor, deformidades y fracturas óseas, aunque muchos casos son asintomáticos. En ocasiones se producen quistes óseos aneurismáticos, hemorragias, compromisos neurológicos y raramente osteosarcomas. Algunos casos se asocian a síndrome de McCune-Albright, síndrome de Mazabraud y a osteomalacia por hipofosfatemia por pérdida tubular renal inducida por el FGF23 producido por el tejido displásico. Los hallazgos en las radiografías convencionales son característicos, aunque variables y de carácter evolutivo. La gammagrafía ósea es la técnica de imagen con mayor sensibilidad para determinar la extensión de la enfermedad. El diagnóstico diferencial incluye múltiples lesiones óseas de características similares y en raras ocasiones se requiere biopsia ósea o estudio genético para confirmarlo. No existe un consenso unánime acerca del abordaje terapéutico de estos pacientes, razón por la cual es necesario un enfoque multidisciplinario. La conducta puede ser expectante o quirúrgica según el tipo de lesiones y es importante el manejo del dolor y de las endocrinopatías asociadas. La mayor experiencia publicada se refiere al uso de bifosfonatos y, más recientemente, denosumab. Los tratamientos actuales son insuficientes para modificar el curso de la enfermedad y es necesario el desarrollo de nuevas moléculas que actúen específicamente en el gen GNAS1 o sobre las células mesenquimales afectadas. (AU)

Fibrous dysplasia of bone is a noninherited developmental anomaly of bone characterized by abnormal proliferation of fibroblasts and differentiation of osteoblasts that cause a replacement of trabeculous bone by fibrous connective tissue. It is caused by a somatic mutation in the GNAS1 gene, which induces an undifferentiated mesenquimal cells activation and proliferation with formation of fibrous tissue and abnormal osseous trabeculae. There are monostotic, polyostotic and craniofacial variants with different grades of bone pain, deformities and fractures, although many cases remain asymptomatic. Aneurysmal bone cysts, bleeding, neurological compromise and infrequently osteosarcoma are possible complications. Some cases are associated to McCune-Albright syndrome, Mazabraud syndrome or hypophosphatemia and osteomalacia due to to renal tubular loss induced by FGF23 produced by dysplastic tissue. The findings on conventional radiography are characteristic although variable and evlolve with time. Bone scintigraphy is the most sensitive technique to evaluate the extent of disease. Differential diagnosis include several osseous lesions of similar appearance and, in some cases, bone biopsy or genetic testing may be necessary. Today, there is no consensus regarding the therapeutic approach for these patients and it is necessary a multidisciplinary medical team. Watchful waiting or surgical interventions can be indicated, depending on the type of bone lesions. Bone pain and associated endocrinopathies management are very important. Most published experience refers to the use of bisphosphonates and, more recently, denosumab. Current treatments are insufficient to modify the natural curse of the disease and therefore, new molecules with specific action on GNAS1 gene or affected mesenchymal cells are necessary. (AU)

Fibrous dysplasia of the temporal bone secondary to ear surgery: a case report.

INTRODUCTION: In this report, we describe the clinical course, diagnostic features and management of a patient with fibrous dysplasia of the temporal bone 7 years after middle ear surgery on the same side. CASE PRESENTATION: A 16-year-old Caucasian girl presented to our hospital with a growing bone lesion in the roof of the left temporal bone. She had undergone a previous tympanoplasty at 7 years of age because of a cholesteatoma. At the time of that first surgery, no radiological or histological signs indicated a bone disorder. A computed tomographic scan of the temporal bone showed a lesion with rarefaction areas and lytic images inside that affected the roof of the cavity to the tegmen tympani without alterations in the inner ear. A surgical revision of the ear cavity was performed by resecting the lesion and regularizing the cavity. The histopathologic study confirmed fibrous dysplasia. The patient progressed satisfactorily after surgery with no evidence of recurrence. CONCLUSION: To the best of our knowledge, this is the first report of fibrous dysplasia of the temporal bone secondary to ear surgery.

Displasia fibrosa monostótica del adulto en maxilar superior: presentación de un caso clínico / Monostotic fibrous dysplasia of the adult in the upper jaw: report of a clinical case

La displasia fibrosa es una patología poco frecuente, benigna, que afecta al tejido óseo. Puede tomar un solo hueso (monostótica) o tomar varios huesos (poliostótica). Se llega al diagnóstico definitivo tras el estudio histopatológico. Se presenta un caso clínico y se realiza la revision bibliográfica correspondiente.

Displasia fibrosa monostótica dos maxilares: revisão da literatura e relato de caso / Fibrous dysplasia of the jaws: report of a case and literature review

A displasia fibrosa é uma alteração óssea benigna do grupo das lesões displásicas na qual ocorre a substituição de tecido ósseo normal por tecido fibroso imaturo. O tipo monostótica consiste no surgimento da lesão em apenas um dos ossos da face, sendo esta forma a mais freqüente e menos severa desta condição. Dos ossos faciais a maxila é a mais afetada. Procedimento cirúrgico conservador e acompanhamento clínico são indicados para o tratamento. O cirurgião deve considerar o período de crescimento ósseo do paciente com o objetivo de evitar as recidivas, que são freqüentes em pacientes tratados precocemente. O presente trabalho relata um caso de paciente do gênero feminino, apresentando a doença na maxila direita, a qual foi submetida a duas cirurgias; a primeira aos 12 anos por desconforto estético, e a segunda, aos 20 anos, por motivo funcional. Os autores propõem estas duas situações como justificativa para o tratamento cirúrgico precoce visto que a recidiva é freqüente, principalmente em pacientes submetidos à cirurgia durante seu estágio de maturação óssea. O tratamento conservador para esses pacientes, sem envolvimento estético grave ou funcional, ainda é o preconizado. Quimioterapia e radioterapia não se apresentam eficazes no controle da lesão

Displasia fibrosa monostótica. Relato de un caso clínico / Monostotic fibrous dysplasia. A clinical case report

La displasia fibrosa (DF) es una patología benigna rara, generalmente asintomática, que afecta el tejido óseo. Debido al remplazo gradual del tejido óseo por tejido fibroso se producen alteraciones óseas estéticas y funcionales. En este artículo se realiza una revisión de la literatura sobre la DF y se relata un caso clínico de un hombre de 33 años de edad que presenta deformidad facial debida al crecimiento lento y progresivo del maxilar(AU)

Fibrous dysplasia (FD) is a rare bening pathology, generally asymptomatic affecting the bone tissue. Due to the gradual replacement of the bone tissue by fibrous tissue, aesthetic and functional bone alterations are produced. A review of the literature on FD is made and it is reported a clinical case of a 33-year-old man presenting facial deformity as a result of the slow and progressive growth.of the jaw(AU)

Cellular and molecular basis of fibrous dysplasia.

Recent advances have been made in the cellular and molecular mechanisms involved in monostotic and polyostotic fibrous dysplasia, a rare nonmalignant disease causing bone deformations and fractures. The molecular basis of fibrous dysplasia has been clarified when mutations affecting the stimulatory alpha subunit of G protein (Gs) have been found in dysplastic bone lesions. The histological analysis of dysplastic lesions revealed that the mutations in Gsalpha caused abnormalities in cells of the osteoblastic lineage and therefore in the bone matrix. Further in vitro analyses of bone cells from mutant dysplastic bone lesions revealed that the abnormal deposition of immature bone matrix in fibrous dysplasia results from decreased differentiation and increased proliferation of osteoblastic cells. Finally, the signaling pathway involved in these osteoblastic abnormalities has been identified. It is now apparent that the constitutive elevation in cAMP level induced by the Gsalpha mutations leads to alterations in the expression of several target genes whose promoters contain cAMP-responsive elements, such as c-fos, c-jun, Il-6 and Il-11. This in turn affects the transcription and expression of downstream genes and results in the alterations of osteoblast recruitment and function in dysplastic bone lesions. These mechanisms provide a cellular and molecular basis for the alterations in bone cells and bone matrix in fibrous dysplasia.

Displasia fibrosa dos maxilares: revisäo da literatura e relato de dois casos / Fibrous dysplasia of the jaws: review of literature and report of two cases

Este trabalho tem como objetivo apresentar uma revisäo da literatura da displasia fibrosa nos maxilares, apresentando os seus principais aspectos clínicos, radiográficos, histopatológicos, assim como as diferentes possibilidades de tratamento e o prognóstico desta condiçäo. Adicionalmente säo relatados dois casos do Departamento de Patologia e Diagnóstico Oral da FO/UFRJ, que estäo sendo acompanhados pelos autores

Etiology of fibrous dysplasia and McCune-Albright syndrome.

In this paper, the etiology of monostotic fibrous dysplasia and McCune-Albright syndrome is explained. Both monostotic fibrous dysplasia and McCune-Albright syndrome are sporadically occurring disorders in which a mutation in the GNAS1 gene occurs postzygotically in a somatic cell. All cells descended from the mutated cell can manifest features of McCune-Albright syndrome or fibrous dysplasia. Cells descended from non-mutated cells develop into normal tissues. Thus, the clinical pattern is variable in distribution and appearance. More generalized vs more localized expression depend on (a) how small or how large the cell mass is during embryogenesis when the mutation occurs and (b) where in the cell mass the mutation occurs. Topics discussed include G proteins and their receptors, cycling of stimulatory G protein between active and inactive forms, and specific mutations in GNAS1. We also discuss four possibilities: (a) Are there masked mutations? (b) Are there effects of imprinting? (c) Are there non-classical mutations? and (d) Is fibrous dysplasia a neoplasm?