Caracterización clínica de pacientes chilenos con displasia fibrosa/síndrome de McCune-Albright / Clinical features of Chilean patients with Fibrous Dysplasia/McCune-Albright Syndrome

BACKGROUND: Fibrous Dysplasia/McCune-Albright Syndrome (FD/MAS) is characterized by a spectrum of manifestations that may include fibrous dysplasia of bone and multiple endocrinopathies. AIM: To describe the clinical spectrum, the study and follow-up of patients with FD/MAS cared at our institution. MATERIAL AND METHODS: Review of medical records of 12 pediatric and adult patients (11 women) who met the clinical and genetic diagnostic criteria for FD/ MAS. RESULTS: The patients' mean age at diagnosis was 4.9 ± 5.5 years. The most common initial clinical manifestation was peripheral precocious puberty (PPP) in 67% of patients and 75% had café-au-lait spots. Fibrous dysplasia was present in 75% of patients and the mean age at diagnosis was 7.9 ± 4.7 years. Ten patients had a bone scintigraphy, with an age at the first examination that varied between 2 and 38 years of age. The most frequent location of dysplasia was craniofacial and appendicular. No patient had a recorded history of cholestasis, hepatitis, or pancreatitis. In four patients, a genetic study was performed that was positive for the pathogenic variant of guanine nucleotide binding protein, alpha stimulating (GNAS). CONCLUSIONS: These patients demonstrate the variable nature of the clinical presentation and study of FD/MAS. It is essential to increase the index of diagnostic suspicion and adherence to international recommendations.

Fibrous dysplasia: rare manifestation in the temporal bone / Displasia fibrosa: manifestação rara no osso temporal

Abstract Introduction: Fibrous dysplasia is a benign disorder, in which normal bone is replaced by fibrosis and immature bone trabeculae, showing a similar distribution between the genders, and being more prevalent in the earlier decades of life. Fibrous dysplasia of the temporal bone is a rare condition, and there is no consensus as to whether it is more common in monostotic or polyostotic forms. External auditory meatus stenosis and conductive dysacusis are the most common manifestations, with cholesteatoma being a common complication, whereas the involvement of the otic capsule is an unusual one. Surgical treatment is indicated to control pain or dysacusis, otorrhea, cholesteatoma, and deformity. Objectives: To describe the clinical experience of a tertiary referral hospital with cases of fibrous dysplasia of the temporal bone. Methods: Sampling of patients diagnosed with fibrous dysplasia of the temporal bone, confirmed by tomography, treated at the pediatric otology and otorhinolaryngology outpatient clinics, between 2015 and 2018. The assessed variables were age, gender, laterality, external auditory meatus stenosis, deformity, hearing loss, presence of secondary cholesteatoma of the external auditory meatus, lesion extension and management. Results: Five patients were included, four females and one male, with age ranging from 13 to 34 years. Three had the polyostotic form and two the monostotic form of fibrous dysplasia of the temporal bone. Four patients had local deformity and external auditory meatus stenosis, two of which progressed to cholesteatoma. All patients showed some degree of hearing impairment. All had preserved otic capsule at the tomography. Two patients are currently undergoing clinical observation; two were submitted to tympanomastoidectomy due to secondary cholesteatoma; one was submitted to lesion resection, aiming to control the dysacusis progression. Conclusion: Five cases of fibrous dysplasia of the temporal bone were described, a rare disorder of which the otologist should be aware.

Resumo Introdução: Displasia fibrosa é uma desordem benigna, na qual o osso é substituído por fibrose e trabeculado ósseo imaturo, com distribuição semelhante entre sexos, mais comum nas primeiras décadas de vida. O acometimento do osso temporal pela displasia fibrosa é raro, não há consenso se é mais comum nas formas monostóticas ou poliostóticas. Estenose do meato acústico externo e disacusia condutiva são as manifestações mais comuns. Colesteatoma é também uma complicação comum e o acometimento da cápsula ótica incomum. O tratamento cirúrgico está indicado para controle de dor ou disacusia, otorreia, colesteatoma, deformidade. Objetivos: Descrever a experiência clínica de hospital terciário de referência com casos de displasia fibrosa do osso temporal. Método: Amostragem dos pacientes com diagnóstico de displasia fibrosa do osso temporal, confirmado pela tomografia, atendidos nos ambulatórios de otologia e otorrinolaringologia pediátrica, entre 2015 e 2018. As variáveis avaliadas foram idade, gênero, lateralidade, estenose do meato acústico externo, deformidade, perda auditiva, presença de colesteatoma secundário de meato acústico externo, extensão da lesão e conduta adotada. Resultados: Foram incluídos cinco pacientes, quatro do sexo feminino e um masculino, de 13-34 anos. Três apresentaram a forma poliostótica da displasia fibrosa do osso temporal e dois a forma monostótica. Quatro apresentaram deformidade local e estenose do meato acústico externo, dois desses evoluíram com colesteatoma. Todos manifestaram algum grau de comprometimento auditivo. Todos apresentaram cápsula ótica preservada na tomografia. Duas pacientes estão em observação clínica; duas foram submetidas a timpanomastoidectomia devido a colesteatoma secundário; um foi submetido a ressecção da lesão para controle de progressão da disacusia. Conclusão: Foram descritos cinco casos de displasia fibrosa do osso temporal, desordem rara para a qual o otologista deve estar atento.

McCune-Albright syndrome - A case report with transmission electron microscopy

Abstract McCune - Albright syndrome is a genetic disease with cutaneous mosaicism caused by post-zygotic activating mutations in GNAS locus, it has a triad of fibrous bone dysplasia, café-au-lait macules and precocious puberty. We examined a 22-year-old female patient with café au lait spot in right side of the abdomen, with a chessboard - like distribution, extending to right thigh with geographical contours, she has also an ovarian cyst, scoliosis and truncal obesity. Biopsies were taken from the hyperpigmented area and processed for light microscopy and for transmission electron microscopy. Light microscopy showed increased melanin pigment with HE staining. Immunohistochemistry with melanocytic markers (HMB-45 and Melan-A) revealed a normal number of melanocytes. Transmission electron microscopy demonstrated normal epidermal structures, such as desmosomes, cytokeratin filaments and hemidesmosomes. With high magnifications an irregular melanossomal contour was seen, with some indentations in their outline.

Is periostin useful as a biomarker for fibrous dysplasia? / ¿Es útil periostina como biomarcador de displasia fibrosa?

Fibrous dysplasia (FD) is an infrequent non-hereditary bone disease caused by a somatic mutation of the GNAS gene. Periostin is a novel marker that increases during tissue healing and fibrous or inflammatory diseases. We conducted an exploratory case-control study to evaluate sensitivity of periostin as a biomarker of FD. The study comprised 15 patients with FD, and healthy age- and sex-matched subjects (controls). Serum periostin levels were assessed and comparisons were established between FD patients and controls, and between patients with the monostotic and the polyostotic form of FD. No statistically significant differences in serum periostin levels were observed between the cohort of FD patients studied here and the control group (FD: 51.1±10ng/ml vs. control: 44.2±15ng/ml; p=0.15), or between the clinical forms of FD (polyostotic: 51.8±9.1ng/ml vs. monostotic: 49.6±13 ng/ml; p=0.66). A sub-analysis performed to compare serum levels of periostin in FD patients with and without a history of fractures showed no statistically significant differences [fracture patients (n=4): 41.2±17ng/ml vs. non-fracture patients (n=11): 49.9±11 ng/ml; p=0.47].Lastly, sensitivity of periostin as a biomarker of FD was analyzed, and was found to have low sensitivity to estimate disease activity [ROC curve; cut-off points: 39.625(0.867-0.467)]. To conclude, in the cohort of FD patients studied here, periostin serum levels did not differ significantly from those of the control group or between the two forms of the disease, and showed low sensitivity as a biomarker of the disease. (AU)

La displasia fibrosa (DF) es una enfermedad infrecuente del hueso, no hereditaria producida por una mutación somática del gen GNAS. Periostina (Postn) es un novedoso marcador, cuyos niveles séricos se encuentran elevados en los procesos de reparación tisular, enfermedades fibrosas o inflamatorias. Llevamos a cabo un estudio exploratorio caso-control para evaluar la sensibilidad de Postn como biomarcador de DF. Se incluyeron en el estudio 15 pacientes con DF apareados por edad y género con sujetos sanos (controles) en los cuales se evaluó los niveles séricos de Postn en pacientes con DF y controles y según forma de presentación clínica. No observamos diferencias estadísticamente significativas en los niveles séricos de Postn y el grupo control (DF: 51.1±10ng/ml vs. control: 44.2±15ng/ml; p=0.15) como así tampoco por forma clínica de DF (poliostótica: 51.8±9.1ng/ml vs. monos-tótica: 49.6±13 ng/ml; p=0.66). Posteriormente realizamos un sub-análisis para evaluar los niveles séricos de Postn en los pacientes con DF y antecedentes de fracturas no observan-do diferencias estadísticamente significativas [fracturados (n=4): 41.2±17ng/ml vs. no frac-turados (n=11): 49.9±11 ng/ml; p=0.47]. Por último analizamos la sensibilidad Postn como biomarcador de DF, mostrando este poseer escasa sensibilidad para estimar actividad de la enfermedad [curva ROC; puntos de corte: 39.625 (0.867-0.467)]. En conclusión, los ni-veles séricos de Postn en nuestra cohorte de pacientes con DF no mostraron diferencias estadísticamente significativas comparadas con el grupo control o por forma clínica de presentación, mostrando una baja sensibilidad como biomarcador de enfermedad. (AU)

Agreement Between Clinical-Radiographic and Histopathological Diagnoses in Maxillofacial Fibro-Osseous Lesions

ABSTRACT Objective: To compare the agreement of clinical and radiographic diagnosis with the histopathological diagnosis in fibro-osseous lesions of the jaws. Material and Methods: An analytical and exploratory study was made based on systematic collected data, carried out in the laboratory of surgical pathology of a public Dental School. There were evaluated cases of fibrous dysplasia (FD), cemento-osseous dysplasia (COD) and ossifyng fibroma (OF), diagnosed by clinical, radiographic (panoramic and periapical radiography), and histopathological analysis, in a period of 12 years (from March 2001 to June 2013). Descriptive and inferential statistics (Fisher's exact test) were obtained. Results: Ninety-six cases of FOLs were evaluated. The radiographic aspects of the FOLs studied did not differ significantly (p=0.09). Radiolucent lesions were the least frequent, corresponding to approximately 13.5% of radiographic findings. Mixed lesions and radiopaques were more present, how they were COD and FD, respectively. The more aggressive variation of OF (Juvenile Ossifying Fibroma - JOF) was less frequent among the pathologies evaluated. In approximately 61.46% of the cases clinical and radiographic diagnosis were confirmed by histopathological diagnosis of FOLs. The highest agreement and the highest disagreement were observed in COD cases (40.7% and 62.2%, respectively). Conclusion: FOLs of the maxillaries represent a group of lesions in which the establishment of the clinical and radiographic diagnosis supported by the histopathological confirmation is critical and challenging.

Síndrome de Mazabraud: reporte de un caso / Mazabraud syndrome: A case report

El síndrome de Mazabraud es una rara asociación de lesiones del sistema musculoesquelético. Resulta de la combinación de uno o varios mixomas intramusculares y displasia fibrosa. Presentamos a un hombre de 46 años con lesiones óseas compatibles con displasia fibrosa asociada a mixoma intramuscular configurando un síndrome de Mazabraud y una revisión de la bibliografía. Nivel de Evidencia: IV

Mazabraud's Syndrome is a rare association of lesions to the musculoskeletal system. It results from the combination of one or more intramuscular myxomas and fibrous dysplasia. We present a case of a 46-year-old man with bone lesions compatible with fibrous dysplasia associated with intramuscular myxoma, configuring Mazabraud's Syndrome and a review of the literature. Level of Evidence: IV

Displasia fibrosa monostótica craneofacial / Craniofacial monostotic fibrous dysplasia

La displasia fibrosa es una enfermedad benigna del hueso, de base genética y de progresión lenta, que se caracteriza por el reemplazo progresivo del hueso normal por tejido fibrótico. El proceso puede afectar un solo hueso o múltiples huesos (displasia fibrosa monostótica o poliostótica); esta última puede estar asociada con enfermedades sindrómicas, como el síndrome de McCune-Albright. Objetivo: revisar el diagnóstico y tratamiento de los pacientes con displasia fibrosa craneofacial. Materiales y métodos: se realizó una revisión de artículos científicos en revistas indexadas en línea como técnica para la recolección de información relevante en bases de datos como SciELO, Google Académico, Scopus, PubMed y DynaMed, con artículos publicados en inglés y español. El período de revisión tuvo como límite el 1 de junio de 2020. Los términos de búsqueda fueron: "displasia fibrosa", "displasia fibrosa monostótica" y "displasia fibrosa craneofacial". Se obtuvieron 33 artículos. Conclusión: la displasia fibrosa monostótica craneofacial es una enfermedad rara que afecta principalmente la mandíbula, el hueso maxilar y el cornete inferior. Puede cursar asintomática o presentar deformidades faciales, dolor y trastornos visuales. Su diagnóstico es principalmente por estudios de imágenes y la biopsia. El tratamiento quirúrgico debe ser bien planeado en cada uno de los pacientes y enfocado a deformidades faciales, se deben evitar los trastornos visuales y es necesario cuando se maligniza la lesión.

Fibrous dysplasia is a slowly progressive, genetically based, benign bone disease characterized by progressive replacement of normal bone with fibrotic tissue. The process can affect a single bone or multiple bones (monostotic or polyostotic fibrous dysplasia); the latter may be associated with syndromic diseases, such as McCune-Albright syndrome. Objective to review the diagnosis and treatment of patients with fibrous craniofacial dysplasia. Materials and methods a review of scientific articles was carried out in online indexed journals as a technique for collecting relevant information in databases such as SciELO, Google Scholar, Scopus, PubMed, and DynaMed, with articles published in English and Spanish. The review period was limited to June 1, 2020. The search terms were: "fibrous dysplasia", "monostotic fibrous dysplasia", and "craniofacial fibrous dysplasia". Obtaining 33 articles. Conclusion craniofacial monostotic fibrous dysplasia is a rare disease, mainly affecting the mandible, the maxillary bone, and the inferior turbinate. It can be asymptomatic or present facial deformities, pain and visual disorders. Its diagnosis is mainly by imaging studies and biopsy. Surgical treatment must be well planned in each of the patients, focused on facial deformities, avoiding visual disorders and is necessary when the lesion is malignant.

Copy number alteration profiling facilitates differential diagnosis between ossifying fibroma and fibrous dysplasia of the jaws / 国际口腔科学杂志·英文版

Ossifying fibroma (OF) and fibrous dysplasia (FD) are two fibro-osseous lesions with overlapping clinicopathological features, making diagnosis challenging. In this study, we applied a whole-genome shallow sequencing approach to facilitate differential diagnosis via precise profiling of copy number alterations (CNAs) using minute amounts of DNA extracted from morphologically correlated microdissected tissue samples. Freshly frozen tissue specimens from OF (n = 29) and FD (n = 28) patients were obtained for analysis. Lesion fibrous tissues and surrounding normal tissues were obtained by laser capture microdissection (LCM), with ~30-50 cells (5 000-10 000 µm

Manejo cirúrgico de sequestro ósseo pósexodontia em paciente portador de displasia cemento-óssea florida: relato de caso / Surgical management of post-exodontia bone sequestral in patients with displasia bone cement-florida: case report

A displasia cemento-óssea florida (DCOF) é uma condição não neoplásica, esclerosante limitada aos ossos maxilares, relacionada ao osso do processo alveolar e, na maioria dos casos envolvendo bilateralmente a mandíbula. É uma condição rara que se apresenta nos maxilares, de forma autolimitante, evoluindo de um estágio osteolítico para osteoblástico, com prevalência pelo gênero feminino, de meia idade a idosas, melanoderma. Dessa forma, o objetivo do trabalho é relatar o caso clínico de uma paciente portadora de displasia cemento-óssea florida apresentando osteomielite local após exodontia.Paciente de 57 anos de idade, melanoderma, compareceu ao ambulatório do Hospital Manoel Victorino (Salvador, BA) do serviço de Cirurgia e Traumatologia Bucomaxilofacial, referindo histórico de exodontia do dente 47 há aproximadamente 02 anos, sem cicatrização local e presença de supuração e odor fétido. Ao exame intrabucal notou- se a presença fístula na região do dente 47 com secreção purulenta espontânea e presença de tecido necrótico. Ao exame de imagem (radiografia panorâmica), foi observado presença de lesões radiopacas multifocais das áreas posteriores mandibulares. Foi submetida a cirurgia, sob anestesia geral, para curetagem de sequestro ósseo e fechamento primário do defeito por primeira intenção e acompanhamento. O objetivo do trabalho foi relatar um caso clínico de um sequestro ósseo mandibular em uma paciente com displasia cemento- óssea florida(AU)

Flowery cementum-bone dysplasia (DCOF) is a non-neoplastic, sclerosing condition limited to maxillary bones, related to the alveolar process bone and, in most cases, bilaterally involving the mandible. When infected can lead to suppuration and kidnapping, resulting in a picture of osteomyelitis. It is a rare condition that occurs in the jaws, in a selflimiting way, evolving from an osteolytic stage to osteoblastic, with prevalence by the female gender, from middle age to the elderly, melanoderma. Therefore, the aim of this paper is to report a diagnosed case of florid cemento-ousseous dysplasia, presenting local osteomyelitis after a extraction. Patient 57 years old, melanoderma, attended the outpatient clinic of the Hospital Manoel Victorino (Salvador, BA) of the Bucomaxillofacial surgery and traumatology department, referring to a history of the right mandible exodontia for approximately 2 years, without local scarring and presence of odor and suppuration fetid The intraoral examination revealed the presence of a fistula in the region distal to the tooth 47 with spontaneous purulent secretion and necrotic tissue. At the imaging examination (panoramic radiography), the presence of multifocal radiopaque lesions of the mandibular posterior areas was observed. She underwent surgery under general anesthesia for curettage of bone sequestration and primary closure of the defect by first intention and follow-up. The objective of this study was to report a clinical case of a mandibular bone sequestration in a patient with florid cementoosseous dysplasia(AU)

Jaffe-Lichtenstein syndrome associated with a simple bone cyst: unprecedented rare case report

Abstract Lesions denominated fibro-osseous lesions of the jaw constitute a diversified group of disorders, in which the normal bone architecture is replaced by fibroblasts, collagen fibers and immature bone. At present, the World Health Organization recognizes four variants of these lesions, namely: bone-cement dysplasia, fibrous dysplasia, ossifying fibroma and Familial gigantiform cementoma. Fibrous dysplasia may present in the monostotic form, affecting one single bone or an isolated craniofacial region; and in the Polyostotic form, involving two or more bones of the skeleton, and eventual association with syndromic conditions. The patient, C.P.G., 43 years old, sought attendance due to symptomatic increase in the region of the mandibular body on the right side. Imaging exams revealed craniofacial areas with ground-glass aspect, beyond the extensive mandibular radiolucent lesion. During the physical exam, spots of the Café au lait type disposed on the right side of the body were identified, in addition to uncoordinated gait with distinct shortening of the right leg. Additional radiographic exams showed evidence of skeletal dissemination of the disease. The patient denied any sexual precocity, and the final diagnosis was fibrous dysplasia, expressed by means of the Jaffe-Lichtenstein syndrome, in association with a simple bone cyst.

Resumo As denominadas lesões fibro-ósseas dos maxilares constituem um grupo diversificado de desordens nas quais a arquitetura óssea normal é substituída por fibroblastos, fibras colágenas e osso imaturo. Atualmente a Organização Mundial de Saúde reconhece quatro variantes destas lesões, sendo elas: a displasia cemento-óssea, a displasia fibrosa, o fibroma ossificante e cementoma gigantiforme familiar. A displasia fibrosa pode ser apresentar na forma monostótica, acometendo um único osso ou a região craniofacial isoladamente, e a forma poliostótica, envolvendo dois ou mais ossos do esqueleto, com eventual associação com condições sindrômicas. Paciente C.P.G., 43 anos, procurou atendimento devido aumento volumétrico sintomático na região de corpo mandibular do lado direito. Exames imaginológicos revelaram áreas craniofaciais com aspecto de vidro fosco ou despolido, além de extensa lesão radiolúcida mandibular. Durante o exame físico foram identificadas manchas do tipo café com leite dispostas do lado direito do corpo, além de marcha descoordenada com nítido encurtamento da perna direita. Novos exames radiográficos evidenciaram a disseminação esquelética da doença. O paciente negou qualquer precocidade sexual e o diagnóstico final foi de displasia fibrosa, expressa por meio da síndrome de Jaffe-Linchtenstein, em associação com um cisto ósseo simples.

Discondrosteosis de Léri-Weill. Presentación de una familia afectada / Léri-Weill dyschondrosteosis. Presentation of an affected family

RESUMEN Fundamentación: La discondrosteosis de Léri-Weill, displasia ósea de origen genético que afecta la región mesomélica con acortamiento de las extremidades, provoca talla baja con extremidades cortas con deformidad de Madelung; esta enfermedad muestra un patrón de herencia autosómico dominante con alta penetrancia. Objetivo: Describir las deformidades de esta discondrosteosis de baja frecuencia con expresividad variable, que se presentó de la misma forma en todos los afectados de esta familia. Presentación de caso: Se reportó una familia con enfermos en tres generaciones con deformidad de Madelung de ambas muñecas y baja estatura de origen mesomélico, que se mantiene seguimiento en consultas de Genética Clínica y Ortopedia. Conclusiones: El examen físico y radiológico imprescindibles para llegar al diagnóstico clínico. El método clínico y la valoración multidisciplinaria resultaron de gran valor para definir esta enfermedad y poder brindar un adecuado asesoramiento genético a esta familia.

ABSTRACT Background: Léri-Weill dyschondrosteosis, bone dysplasia of genetic origin that affects the mesomelic region with shortening of the extremities, causes short stature with short extremities with Madelung deformity.This disease shows an autosomal dominant inheritance pattern with high penetrance. Objective: To describe the deformities of this low frequency dyschondrosteosis with variable expressivity which was presented in the same way in all those affected in this family. Case presentation: A family with sick members was reported in three generations with Madelung deformity of both wrists and short stature of mesomelic origin which is followed up in consultations of Clinical Genetics and Orthopedics. Conclusion: The essential physical and radiological examination to reach the clinical diagnosis. The clinical method and the multidisciplinary assessment were of great value to define this disease and to be able to provide adequate genetic counseling to this family.

Displasia fibrosa de columna lumbar en una mujer de mediana edad: Presentación de un caso / Fibrous dysplasia of the lumbar spine in a middle-aged woman. Case presentation

La displasia fibrosa es una lesión ósea benigna caracterizada por el desarrollo anormal del tejido fibroso de disposición arremolinada, con trabéculas de hueso inmaduro no laminar. Se distinguen dos formas: monostótica y poliostótica. El compromiso de columna vertebral se asocia, con más frecuencia, a la variedad poliostótica; la forma monostótica es infrecuente. Presentamos a una mujer de 46 años que consultó por lumbocruralgia derecha de dos meses de evolución, con diagnóstico definitivo de displasia fibrosa de columna lumbar. Los estudios por imágenes mostraron una lesión monostótica lítico-quística con tabiques internos localizada en el arco posterior de la quinta vértebra lumbar. Sus características en los estudios por imágenes sugirieron un quiste óseo aneurismático, mientras que la anatomía patológica fue reveladora frente al diagnóstico final de displasia fibrosa. Los síntomas menores y la ausencia de complicaciones llevaron a indicar un tratamiento conservador. Si bien el compromiso de columna lumbar por displasia fibrosa monostótica es infrecuente, debería considerarse entre los diagnósticos diferenciales de una lesión lítica solitaria en dicha localización. No obstante, no se descarta mediante histopatología que pueda tratarse de un caso de coexistencia de displasia fibrosa y quiste óseo aneurismático o que la displasia fibrosa se haya desarrollado sobre un quiste óseo aneurismático. Nivel de Evidencia: IV

Fibrous dysplasia (FD) is a benign skeletal disorder characterized by abnormal development of fibrous tissue in a whorled pattern and containing trabeculae of immature non-lamellar bone. FD has two forms of clinical presentations: monostotic and polyostotic. Spinal involvement is seen mostly in the polyostotic form and is very unusual in the monostotic form. We present a 46-year-old woman that complained of right low back pain with a 2-month evolution. The definitive diagnosis was FD of the lumbar spine. Imaging testing revealed a lytic-cystic monostotic lesion with internal septa located in the posterior arch of the fifth lumbar vertebra, suggestive of Aneurysmal Bone Cyst (ABC). However, the anatomical pathology revealed FD as the final diagnosis. Conservative treatment was undertaken due to minimal symptoms and the absence of complications. Although monostotic FD of lumbar spine is rare, it should be taken into account among the differential diagnoses of a single osteolytic lesion. However, histopathology testing cannot rule out the coexistence of FB and ABC or a setting of FB secondary to an ABC. Level of Evidence: IV

Nuevos avances en el conocimiento de la historia natural de la displasia fibrosa / News advances in the knowledge of natural history of the fibrous dysplasia

La displasia fibrosa (DF) es una enfermedad infrecuente del hueso, no hereditaria, producida por una mutación activadora del gen GNAS, responsable de codificar la unidad a-estimuladora de la proteína G (Gsa). La presentación clínica de la enfermedad es muy variada, pues adopta desde formas asintomáticas hasta otras marcadamente sintomáticas. En los últimos años, el análisis exhaustivo de bases de datos de pacientes con DF ha permitido conocer más sobre su historia natural. En este artículo se revisa la información actualmente disponible sobre algunos aspectos que ayudarán al mejor enfoque clínico del paciente, como son: la utilidad clínica de los marcadores óseos, los factores pronósticos para el desarrollo de fracturas, la DF como condición predisponente para el desarrollo de tumores específicos, nuevas perspectivas sobre la fisiopatología del dolor óseo y nuevas estrategias terapéuticas. Un mayor conocimiento sobre la historia natural de esta enfermedad finalmente redundará en la mejor calidad de vida de los pacientes con DF. (AU)

Fibrous dysplasia (FD) is an infrequent, non-hereditary bone disease caused by a somatic mutation of the GNAS gene, responsible for encoding the a-subunit of the G-protein (Gsa). The clinical presentation of the disease varies greatly, with some patients being asymptomatic and others markedly symptomatic. The exhaustive analysis of the database from patients with FD has allowed to learn more about the natural history of this disease. This article reviews the current information available on the clinical utility of bone markers, the prognostic factors for the occurrence of fractures, the evidence supporting as a predisposing condition for the development of specific tumors, new perspectives on the pathophysiology of bone pain, and emerging therapeutic strategies. A greater understanding of the natural history of this disease will allow to make better medical decisions, which will ultimately contribute to improve FD patients' quality of life. (AU)

Conservative Treatment of Chronic Osteomyelitis Associated with Florid Osseous Dysplasia / Tratamiento Conservador de la Osteomielitis Crónica Asociada con Displasia Ósea Florida

ABSTRACT: Florid osseous dysplasia (FOD) is an extensive form of osseous dysplasia where normal trabecular bone is substituted by fibrous connective tissue and amorphous mineralized tissue. Usually, the lesions are mainly asymptomatic and the patients should be followed with clinical and imaging examination, requiring no intervention. Nevertheless, due to the poor vascularization of the lesion and to local trauma, secondary infections and osteomyelitis may occur. Patients may present with pain, mucosal ulceration, lesion exposure in the oral cavity, fistula and swelling. In such cases, the correct diagnosis and management of the lesion is decisive to reestablish patient's health and quality of life. The aim of this article is to present a case of complicating secondary chronic osteomyelitis treated successfully with conservative intervention. A 68-year-old black female patient reported a "swelling of the gums" that was present for eleven years, with episodes of periodic pain and swelling. On physical examination, a papule with suppuration in the alveolar mucosa in the right side of the mandible was observed. Panoramic radiography and CBCT showed a mixed lesion surrounded by sclerotic bone. The patient was diagnosed with chronic osteomyelitis in association with FOD and treated with antibiotic therapy together with surgical curettage. The incidence, etiophatology, differential diagnosis, treatment and prevention of secondary osteomyelitis associated with FOD are discussed in the light of literature. This information might assist the dentists while choosing the best treatment options for similar cases.

RESUMEN: La displasia ósea florida (DOF) es una forma de displasia ósea donde el hueso trabecular normal es sustituido por tejido conectivo fibroso y tejido mineralizado amorfo. En general, las lesiones son de origen asintomático y los pacientes deben ser seguidos con el examen clínico. Sin embargo, debido a la pobre vascularización de la lesión y al trauma local, pueden producirse lesiones secundarias y osteomielitis. Los pacientes pueden presentarse con dolor, ulceración mucosa, lesión de exposición en la cavidad oral, fístula y edema. En estos casos, el correcto diagnóstico y tratamiento de la lesión es decisivo para reestabilizar la salud y la calidad de la vida. El objetivo de este artículo consistió en presentar un caso de complicación secundaria crónica de osteomielitis tratados con tratamiento conservador. El paciente, negro, de 68 años de edad, consulta por "hinchazón de las encías" que se presentó durante once años, con episodios de dolor. En el examen intraoral, se observó una pápula con supuración en la mucosa alveolar en el lado derecho de la mandíbula. La radiografía panorámica y CBCT mostraron una lesión mixta rodeada de hueso esclerótico. El paciente fue diagnosticado con osteomielitis crónica en asociación con DOF y fue tratado con tratamiento antibiótico junto con curetaje quirúrgico. La incidencia, la etiopatología, el diagnóstico diferencial, el tratamiento y la prevención de la osteomielitis secundaria asociada con DOF se discuten a la luz de la literatura. Esta información puede ayudar a los dentistas a elegir las mejores opciones de tratamiento para casos similares.

Displasia cemento-óssea florida: relato de dois casos tratados por diferentes abordagen / Florid cemento-osseous dysplasia: report of two cases treated with different approaches

Objetivo: relatar dois casos de displasia cemento-óssea florida, descrevendo a evolução clínico-radiográfica ao longo de 5 anos em um paciente assintomático e a abordagem cirúrgica em um caso sintomático. Relato de caso 1: paciente, melanoderma, sexo feminino, 56 anos de idade, encaminhada ao Serviço de Cirurgia Bucomaxilofacial da Universidade Federal da Bahia, por cirurgião-dentista clínico que notou alterações imagiológicas em radiografia panorâmica de rotina. Apesar da importante extensão da lesão em maxila e mandíbula, não havia qualquer sintoma ou sinal clínico de infecção. A paciente foi acompanhada durante 5 anos, com exames de imagem bianuais e medidas clínicas profiláticas. Relato de caso 2: paciente, melanoderma, sexo feminino, 57 anos, apresentou-se ao ambulatório de cirurgia queixando-se de atraso em cicatrização após remoção de um dente. A radiografia panorâmica e a tomografia computadorizada, em conjunto com dados clínicos, permitiram o diagnóstico de displasia cemento-óssea florida com infecção secundária. A paciente foi abordada por meio de osteotomia em região do defeito em mandíbula. A análise microscópica do espécime obtido confirmou a alteração displásica cementoide. Os sinais e sintomas regrediram e a paciente segue em acompanhamento. Considerações finais: a displasia cemento-óssea florida, portanto, é uma doença pouco frequente, cujas manifestações podem demandar diferentes abordagens. É importante o domínio clínico do cirurgião-dentista, uma vez que o diagnóstico equivocado pode guiar a escolhas terapêuticas com resultados insatisfatórios. (AU)

Objective: the objective of this article is to report two cases of florid cemento-osseous dysplasia describing the clinical-radiographic evolution over 5 years in an asymptomatic patient and the surgical approach in a symptomatic one. Case report 1: patient, melanoderma, female, 56 years old, referred to the service by a clinical Dentist who noticed imaging alterations in a routine panoramic radiography. Despite the important extension of the maxillary and mandibular lesion, there was no clinical sign or symptom of infection. The patient has been followed for 5 years with biannual imaging exams and prophylactic clinical measures. Case report 2: patient, melanoderma, female, 57 years old, presented to the surgery outpatient complaining of delay in healing after removal of a tooth. Panoramic X-ray and Computed Tomography together with clinical data allowed the diagnosis of florid cemento-osseous dysplasia with secondary infection. The patient was approached through osteotomy in the region of the mandible defect. The microscopic analysis of the specimen confirmed the dysplastic cementenoid alteration. Signs and symptoms regressed and the patient is in follow up. Final considerations: florida cementoosseous dysplasia is an infrequent disease, whose manifestations may require different approaches. The clinical domain of the Dentist is important, since misdiagnosis can lead to therapeutic choices with unsatisfactory results. (AU)

Craniofacial Polyostotic Fibrous Dysplasia Initially Diagnosed in a Primary Care Unit / 가정의학회지

Fibrous dysplasia (FD) is a non-malignant bone tumor that typically behaves as a slow and indolent growing mass lesion. We report the case of a female patient presenting with headache and facial deformity and later diagnosed with polyostotic fibrous dysplasia (PFD). A 29-year-old woman visited Mealhada Primary Health Care Unit complaining of headache, nasal congestion, and hyposmia for several weeks. She also presented with facial deformity and painful swelling of the upper left orbit. X-ray imaging revealed a suspicious opacity in the left frontal sinus and a right shift of the nasal septum. Computed tomography and bone scintigraphy later confirmed a tumor involving the ethmoid and frontal bone. The patient was referred to the neurosurgery and otorhinolaryngology departments of a central hospital and the suspected diagnosis of PFD was confirmed. A watchful waiting approach with regular imaging screenings was proposed and accepted by the patient, who is now free of symptoms and more acceptant of the benign condition of her tumor. With this case, we aim to make family physicians more aware of this rare but relevant condition that can be difficult to diagnose. FD is a rare but benign tumor that occurs mainly in adolescents and young adults. Symptoms depend on the location and type of the tumor and include facial deformity, vision changes, nasal congestion, and headache. No clear guidelines exist for its treatment, and options include monitoring the progression of the tumor, in addition to medical or surgical approaches.

Análise de imagem de lesões fibro-ósseas / Fibro-osseous lesions image analysis

As lesões fibro-ósseas (LFOs) caracterizam-se pela substituição do osso normal por tecido conjuntivo fibroso e material mineralizado. Displasia fibrosa, fibroma ossificante e displasia cemento-óssea (DCO) compõem este grupo, que além da semelhança histopatológica, pode sobrepor características radiográficas. A correlação de dados clínicos, radiográficos e histopatológicos é necessária para o diagnóstico definitivo. Este trabalho teve como objetivo descrever e avaliar exames odontológicos de imagem de indivíduos diagnosticados com LFOs. Foram desenvolvidos três estudos com metodologias independentes. O primeiro estudo avaliou os efeitos da displasia cemento-óssea em estruturas anatômicas adjacentes por meio de tomografia computadorizada de feixe cônico (TCFC). Foram avaliados 60 casos de DCO, com 244 áreas de lesão envolvendo 426 dentes. A maioria das lesões apresentou aproximadamente 10 mm de diâmetro. Afilamento (n=80) expansão (n=62) e perfuração (n=60) foram os efeitos comuns na cortical óssea. A lâmina dura e o espaço do ligamento periodontal foram descontínuos em todos os dentes. No segundo estudo, 50 radiografias panorâmicas de mulheres com diagnóstico de DCO foram pareadas por idade com 50 radiografias panorâmicas de mulheres sem DCO. Os grupos DCO e não-DCO foram comparados através do índice de espessura da cortical mandibular (ECM), a dimensão fractal (DF) da região de osso trabecular e cortical e o índice cortical mandibular (ICM). O índice de ECM do grupo DCO foi de 3,12 mm (2,15-4,55) e do grupo não-DCO foi 3,52 mm (1,90- 4,70) com diferença estatística entre os grupos (p=0,034). A DF do trabeculado ósseo alveolar normal foi semelhante nos dois grupos, enquanto que menores médias de DF no osso cortical foram encontradas no grupo DCO (p=0,046). A classificação C3 do ICM foi mais comum no grupo DCO (p=0,009). O terceiro foi um estudo preliminar que avaliou a DF em imagens bidimensionais e tridimensionais de TCFC de seis casos de displasia fibrosa e seis de fibroma ossificante. Cortes de reconstrução panorâmica, axial, coronal e sagital foram selecionados em quatro espessuras: 0,25; 5; 15 e 25 mm, e avaliados em 3 formatos de regiões de interesse (RI). Duas metodologias compararam quatro formatos de volumes do interior das lesões. A média de DF das imagens bidimensionais de reconstrução panorâmica e axiais, com 0,25 mm de espessura mostrou diferença significativa entre displasia fibrosa e fibroma ossificante (p<0.05), independente do formato da RI (p>0,05). A média da DF de imagens tridimensionais foi diferente entre os grupos de lesões para a maioria das comparações (p<0.05), independente da metodologia usada. Informações detalhadas sobre a lesão e o envolvimento de estruturas adjacentes podem ser visualizadas em TCFC. Métodos não invasivos como os índices radiomorfométricos e análise fractal podem ser úteis na detecção de baixa densidade mineral óssea, ou mesmo como possível ferramenta de estudo da complexidade de imagens de LFOs.

Fibro-osseous lesions (FOLs) are characterized by the replacement of normal bone with fibrous connective tissue and mineralized material. The group includes the fibrous dysplasia, ossifying fibroma and cemento-osseous dysplasia (COD). These three lesions show similar histopathological and radiographic features. Clinical, radiographic and histopathological data correlation is necessary for the definitive diagnosis. This study aimed to describe and to evaluate dental imaging exams of individuals diagnosed with FOLs. Three studies with independent methodologies were developed. The first study evaluated the effects of COD on the adjacent anatomical structures by means of cone beam computed tomography (CBCT). Sixty cases of COD were evaluated. The assessment of the 60 cases involved 244 lesion areas and 426 teeth. Most lesions presented nearly 10 millimeters (mm) of diameter. Thinning (n=80), expansion (n=62) and perforation (n=60) were common effects on the cortical bone. All 426 teeth presented discontinuation of the lamina dura and of the periodontal ligament space. In the second study, 50 panoramic radiographies of women diagnosed with COD were matched with 50 panoramic radiographies of women without COD according to the individuals' age. Comparisons between groups regarding the mandibular cortical width index (MCW), the fractal dimension (FD) of the region of the trabecular and the cortical bone and the mandibular cortical index (MCI) were carried out. The MCW of the COD group was 3.12 mm (2.15-4.55) and the MCW of the non-COD group was 3.52 mm (1.90-4.70). A significant difference between groups was observed (p=0.034). FD of the normal trabecular alveolar bone was similar in both groups. For the cortical bone, a lower mean FD was observed in the COD group (p=0.046). The MCI C3 was more common in the COD group (p=0.009). The third was a preliminary study, in which the FD was evaluated on twodimensional and three-dimensional CBCT images of six cases of fibrous dysplasia and six cases of ossifying fibroma. Panoramic reconstruction, axial, coronal and sagittal slices were selected in four thicknesses (0.25, 5, 15 and 25 mm) and evaluated in three shapes of regions of interest (ROI). Two methodologies compared four volume formats from inside the lesions. A significant difference between fibrous dysplasia and ossifying fibroma was observed for the mean FD of the twodimensional images of panoramic reconstruction and axial slices with a thickness of 0.25 mm (p<0.05), regardless of the ROI shape (p>0.05). The mean DF of threedimensional images was different between lesion groups for most comparisons (p <0.05), regardless of the methodology used. Detailed information on lesions and involvement of adjacent structures can be viewed in CBCT. Non-invasive methods, such as radiomorphometric indices and fractal analysis may be useful in the detection of low bone mineral density or as a helpful tool for the differentiation of distinct types of FOLs.

Zoledronic acid effect on bone of growing rats / Efecto del ácido zoledrónico en el hueso de ratas en crecimiento

Zoledronic acid (ZA) is an antiresorptive drug used in children with bone diseases like osteogenesis imperfecta, juvenil osteoporosis, fibrous dysplasia and primary bone tumors. The aim of the present study was to evaluate the effects of ZA dose accumulation on growing bone during different periods of treatment in normal rats. Methods: A 4x2 factorial design was used to study the effect of the dose of ZA (D: 0-2.5-12.5-25 µg Z/kg body weight/s.c. weekly) and the length of treatment (T: 15-30 days) in normal female Sprague Dawley rats. Bone morphometric, histomorphometric, densitometric and biomechanical studies were performed. Results: Femoral length and cross-sectional area were affected by both D and T. A significant interaction between D and T was observed in length with a lower value at higher dose and 30 days of treatment. Growth plate of the tibia showed a decrease in total thickness with D and T. Histomorphometric and connectivity parameters of trabecular bone were significantly increased with D and several parameters were also affected by T. Cortical bone strength was increased only with T. Biomechanical parameters of trabecular bone showed significant interaction with greater effect at higher D and T. Conclusion: Even though a mild negative effect of the highest dose of ZA on linear and appositional growth was observed, the other bone parameters evaluated were improved. A careful risk/benefit analysis would lead us to conclude that the mild deleterious effects of ZA during growth are outweighed by the benefit obtained with treatment. (AU)

El ácido zoledrónico (AZ) es un fármaco antirresortivo utilizado en niños con enfermedades óseas como osteogénesis imperfecta, osteoporosis juvenil, displasia fibrosa y tumores óseos primarios. El objetivo del presente estudio fue evaluar los efectos de las dosis acumuladas de AZ en el hueso en crecimiento de ratas hembras normales durante diferentes períodos de tratamiento. Métodos: se utilizó un diseño factorial de 4x2 para estudiar el efecto de la dosis de AZ (D: 0-2,5-12,5-25 µg Z / kg de peso corporal /sc semanalmente) y el período de tratamiento (T: 15-30 días) en ratas Sprague Dawley. Se realizaron estudios óseos morfométricos, histomorfométricos, densitométricos y biomecánicos. Resultados: la longitud y el área de sección transversal del fémur se vieron afectadas tanto por D como por T. Se observó una interacción significativa entre D y T en la longitud obteniéndose un valor más bajo a la dosis más alta y a 30 días de tratamiento. El cartílago de crecimiento de la tibia mostró una disminución en el espesor total con D y T. Los parámetros histomorfométricos y de conectividad del hueso trabecular aumentaron significativamente con D y varios parámetros también se vieron afectados por T. La fortaleza ósea cortical aumentó solo con T. Los parámetros biomecánicos del hueso trabecular mostraron una interacción significativa con un mayor efecto a mayor D y T. Conclusión: a pesar que se observó un leve efecto negativo de la dosis más alta de AZ sobre el crecimiento lineal y aposicional, el resto de los parámetros óseos evaluados mejoraron. Un análisis cuidadoso del riesgo /beneficio permite concluir que los efectos negativos leves del AZ durante el crecimiento son superados por el beneficio obtenido con el tratamiento. (AU)

Prótesis tumoral de cadera en displasia fibrosa de fémur proximal. Informe de un caso / Tumor hip prosthesis in fibrous dysplasia of proximal femur. Case report

Resumen: Antecedentes: La displasia fibrosa se caracteriza por la formación de tejido fibroso inmaduro que genera trabéculas mal formadas. Su afectación puede ser monostótica o poliostótica. Caso clínico: Femenino de 30 años con displasia fibrosa de cadera izquierda. A los 15 años sufre fractura de la misma cadera sin trauma aparente, manejada conservadoramente y con acortamiento importante de la misma extremidad. A los 30 años de edad se embaraza, presenta dolor en cadera izquierda y se exacerba la deformidad y el acortamiento. La radiografía simple muestra deformidad en «cayado de pastor¼, se manejó con bifosfonatos y la tomografía corrobora los hallazgos anteriores. Posteriormente sufrió caída con fractura subtrocantérica de cadera izquierda en sitio de displasia, imagen de vidrio despulido de apariencia quística que involucra el cuello femoral, zona trocantérica y subtrocantérica. Se colocó prótesis tumoral de cadera izquierda, a los cuatro meses mostró evolución favorable. Conclusión: La prótesis tumoral femoral reduce la deformidad, mejora la longitud y disminuye el dolor en pacientes con resección de displasia fibrosa de cadera.

Abstract: Background: Fibrous dysplasia is characterized by the formation of fibrous tissue that generates immature malformed trabeculae. Their involvement may be monostotic or poliostotic. Case report: Thirty years old female with fibrous dysplasia of the left hip. At age 15 suffered hip fracture without apparent trauma, she was managed conservatively and significant shortening of the same limb was observed. At 30 years old, is pregnant, it had left hip pain, deformity and shortening is exacerbated. Simple radiography showed «shepherd's crook deformity¼, she was treated with bisphosphonates. Computed axial tomography corroborates previous findings. She subsequently underwent subtrochanteric fracture fall with left hip dysplasia site, ground glass image of cystic appearance involving the femoral neck, trochanteric and subtrochanteric area. Tumor prosthesis of the left hip was implanted, four months evolution was favorable. Conclusion: Modular hip prosthesis system, reduces deformity, improves length and reduces pain in patients with resection of fibrous dysplasia of the hip.

Importância dos aspectos imaginológicos no plano de tratamento da displasia óssea florida: relato de caso / Importance of imaginological aspects in the florid osseous Dysplasia treatment plan: case report

A displasia óssea florida (DOFL) é uma lesão fibro-óssea relativamente incomum dos maxilares, que acomete, principalmente, mulheres melanodermas de meia idade e geralmente é diagnosticada em radiografias de rotina. O presente trabalho tem como objetivo relatar o caso de uma paciente de 50 anos de idade, melanoderma, encaminhada ao Curso de Odontologia da Universidade Federal do Ceará para avaliação imaginológica. Clinicamente, não foi observada nenhuma alteração de volume de estruturas faciais ou intraorais. A radiografia panorâmica evidenciou imagens radiopacas circunscritas por halos radiolúcidos, localizadas bilateralmente em região edêntula de corpo mandibular, sugestivas de DOFL. Na tomografia computadorizada de feixe cônico (TCFC), observaram se áreas hiperdensas em regiões mandibulares edêntulas, sem expansão de corticais ósseas vestibulares e linguais, e recobertas por fina espessura de tecido ósseo, típicos da displasia. Diante do diagnóstico clínico-imaginológico de DOFL, a paciente foi encaminhada para tratamento odontológico multidisciplinar. Por meio da TCFC, foi possível se estabelecer um plano de tratamento que consistiu em procedimentos minimamente intervencionistas, considerando os aspectos clínicos e imaginológicos das lesões observadas. Em sumário, o presente trabalho reforça a importância do exame clínico meticuloso aliado à avaliação por meio de TCFC, com fins de embasar um plano de tratamento adequado em casos de DOFL assintomáticos... (AU)

Florid osseous dysplasia (FOD) is a fibrous lesion relatively uncommon of maxillary bones, mainly affects middle-age black women and generally is diagnosed on routine radiographs. This paper aims to report a case of black woman, aged 50 years, referred to Dentistry Faculty of Federal University of Ceará for imaging evaluation. Clinically, there were no facial or intraoral structures alterations. Panoramic radiography showed radiopaque images circumscribed by radiolucent halos, located bilaterally in the edentulous mandibular body region suggestive of FOD. Cone beam computed tomography (CBCT) showed hyperdense areas in edentulous mandibular regions, with no expansion of buccal and lingual cortical bone, and covered by fine thickness of bone tissue, characteristic of FOD. After the clinical-imaging diagnosis of FOD, the patient was referred for multidisciplinary dental treatment. Through the CBCT, it was possible to establish a treatment plan that consisted of minimally interventional procedures considering the clinical and imaging limits of the observed lesions. In summary, the present case emphasizes a meticulous clinical examination along with an evaluation by means of CBCT allowing an adequate treatment plan for asymptomatic FOD... (AU)