Denosumab Therapy in Cherubism.

Cherubism is a rare disorder characterized by proliferative fibro-osseous lesions that result in bilateral bony hyperplasia of the face. Management varies based on symptom severity and includes longitudinal follow-up, pharmacotherapy, and/or surgical debulking. Off-label treatment with denosumab, a human monoclonal antibody that binds RANKL and inhibits osteoclast function to reduce bone resorption, can be beneficial in suppressing the proliferation of bone to minimize the need for surgery and to control postoperative reproliferation. Close follow-up is needed to maintain appropriate electrolyte levels. The present case demonstrates the achievement of symptomatic control with denosumab in a child with severe refractory cherubism.

Surgical Treatment of Cherubism With the Use of ThreeDimensional Virtual Planning and CAD-CAM Resection Guides: A Case Report and Systematic Literature Review.

ABSTRACT: We report the use of a three-dimensional virtual surgical planning technique including both fusion and superimposition to obtain harmony and symmetry of the face in an 18-year-old woman suffering from cherubism. The treatment contained several threedimensional techniques that allowed precise planning and a predictable surgical outcome. The reduction plasty was successful, and the postoperative healing was uneventful. No relapse of the disease occurred after the surgical treatment and the sensation of the mentalis area recovered. The patient was satisfied with the aesthetic result and no additional surgery was needed. The surgical planning techniques described, and the CAD/CAM patient-specific resection guides seems to be safe and reliable in a one-step surgical treatment of cherubism patients after the disease has clearly ceased based on radiological findings. A systematic review of the literature on surgical correction of deformities due to cherubism was conducted. The systematic review of the existing literature was performed on the available studies from PubMed and Ovid Medline published before June 9, 2020. The search term was ''Cherubism.'' The inclusion criteria were: 1) full article published in English and 2) the patient had surgical treatment. We excluded the cases that included only minor surgery as biopsy or only treatment of unerupted teeth. The database identified 638 citations of which 50 met the eligibility criteria. The systematic review revealed no earlier use of surgical 3D planning in the treatment of cherubism.

Crecimiento mandibular bilateral: un caso de querubismo / Bilateral swelling of the jaws: a case of querubism

El querubismo es una displasia ósea benigna de la infancia caracterizada por un crecimiento mandibular bilateral progresivo. Presenta herencia autosómica dominante y es más frecuente en varones. Las primeras manifestaciones aparecen en torno a los dos años de edad, con un crecimiento óseo acelerado a los 8-9 años e interrupción espontánea tras la pubertad. El diagnóstico se basa en la clínica, radiología y anatomía patológica. El tratamiento es controvertido, incluyendo tratamiento médico o quirúrgico. Presentamos el caso de un varón de nueve años que consultó por crecimiento mandibular bilateral, requiriendo finalmente extirpación quirúrgica de las lesiones (AU)

Cherubism is a benign bone dysplasia characterized by bilateral progressive enlargement of the jaws. It is an autosomal dominant disease and boys are more affected than girls. The first signs of manifestation of the disease are generally observed at about two years of age, followed by accelerated growth from 8-9 years of age and spontaneous interruption after puberty. The diagnosis is based on clinical, radiographic and histopathologic findings. Treatment is a controversial issue and therapy strategies include surgical treatment and medical treatment. We describe the case of a nine-year-old boy with bilateral swelling of the jaws who required surgical treatment. (AU)

Innovative Surgical Treatment of Severe Cherubism.

BACKGROUND: Cherubism is an autosomal dominant syndrome characterized by excessive bilateral maxillomandibular bony degeneration and fibrous tissue hyperplasia. Conservative management is the preferred treatment as cherubism has a self-limiting course. Functional or emotional disturbances may, however, demand surgical intervention. We report a patient who underwent surgical intervention. METHOD/DESCRIPTION: He had significant enlargement of lower cheeks and bilateral lower lid scleral show. On computed tomography of the face, the patient had significant fibrous tissue involving bilateral maxilla and mandible. The mandibular tumor was excised. Given normal inferior border, bilateral sagittal split osteotomy was performed to infracture and inset the outer cortex. During the procedure, patient required blood transfusion intraoperatively, so the maxillary portion of the procedure was delayed until 6 months later. For the maxilla, bilateral transconjunctival approach was used to resect parts of the orbital floors that were concave, resulting in 1 × 2 cm defects bilaterally which were reconstructed using resorbable plates. Then the anterior maxillary tumor was excised. RESULTS: The patient and his parents were satisfied with his appearance after surgery. The patient was noted to have improvement in contour and decreased scleral show. He has most recently followed up 15 months after the initial surgery. There were no long-term complications. CONCLUSIONS: Severity of cherubism influences the type of surgical intervention. The present case is innovative because this is the first reported case of recontouring orbital floors with resorbable plates and infracturing of the mandible using sagittal split osteotomies for surgical treatment of cherubism.

Defining a new aggressiveness classification and using NFATc1 localization as a prognostic factor in cherubism.

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.

Cherubism: A Case Report with Surgical Intervention.

Cherubism is a rare benign, autosomal-dominant hereditary fibro-osseous condition predominantly affecting the jaws. Symmetrical cyst-like expansions of the jaws cause the characteristic facial swellings. The disease is often associated with severe malposition of teeth. The gene for cherubism is src homology 3 binding protein 2 (SH3BP2) located on chromosome 4p16.3. The repeated experience of this self-limiting disorder in affected individuals published in the medical literature has resulted in a wait-and-see strategy regarding therapeutic options. Indeed, cessation and regression of even large bone expansions can be expected in early adulthood. Nevertheless, severe facial disfiguring and functional impairment can make surgical intervention necessary. This report details the surgical procedures carried out in a patient with progressive and disfiguring jaw expansions at the end of adolescence, the mutation of SH3BP2 gene, and the limited effect of surgically assisted orthodontic tooth movement in a patient with disease-associated impaired tooth development and tooth eruption.

Ophthalmic manifestations of cherubism.

Cherubism is a rare craniofacial disorder characterized by progressive replacement of mandibular and maxillary bone with multicystic fibro-osseous tissue, potentially resulting in significant deformity and morbidity. The severity of the disorder is variable; more advanced disease may affect the orbit and impact vision. We detail the ophthalmological findings in 2 patients, 7 and 8 years of age, with cherubism.

Onlay bone augmentation and bilateral open sinus lifting with simultaneous implant placement in a cherubic patient.

A 20-year-old edentulous woman, who was previously treated with the shave of the inferior border of the mandible and malar prominent region for aesthetic facial contouring, was selected for full mouth rehabilitation of the maxillomandibular region. The patient was treated with bilateral open sinus lifting through a lateral approach in the posterior of the maxilla and an onlay bone graft with lateral ramus as a donor site in the mandible anterior. Eight implants in the maxilla and 7 in the mandible were inserted, and implant-supported prostheses were fabricated. The 18-month follow-up showed good bone condition that suggests graft interventions and implant treatment as a good treatment modality for patients with cherubism.

Orthodontic treatment in cherubism: an overview and a case report.

INTRODUCTION: Cherubism is a rare hereditary disease that frequently manifests as a painless enlargement of the mandible and/or maxilla. The disease usually progresses rapidly during the first and second decades of life but it is self-limiting and often regresses. Although few orthodontic case reports describing cherubic patients exist, the timing and extent of surgical intervention is controversial. AIM: This present paper aims to review the treatment literature and provide a case report of a patient who underwent orthodontic/surgical management. METHODS: The patient presented with severe cherubism in her late teenage years; her main complaint was poor facial and dental appearance. Multiple teeth were missing and those present demonstrated significant preoperative root resorption. Treatment consisted of orthodontic alignment of the upper anterior teeth and a recontouring osteotomy. RESULTS: Confirmed by the patient, the combination approach led to a significant improvement in facial aesthetics and better self-esteem. Tooth movement through the osseous lesions was uneventful and no further root resoption was observed. CONCLUSION: Orthodontic treatment may be undertaken in those affected by Cherubism even with pre-existing idiopathic root resorption, but patients need to be appropriately informed and consented.

[Cherubism: a case followed for 18 years]. / Chérubisme : à propos d'un cas suivi pendant 18ans.

Cherubism is a rare and benign bone disease affecting the bones of the face, mainly the mandible, sometimes the maxilla and exceptionally the whole skeleton. The physiopathology is briefly mentioned, especially the genetic aspect of the disease. Subsequently, we present the case of a patient suffering from cherubism, a case we have been following from the age of four and a half to the age of 22. Each step of the surgical treatment is illustrated through a wide iconography. The discussion analyses the intellectual process that leads to diagnosis. The clinical examination is fundamental, as well as the radiological check-up but the latter may not be feasible due to the young age of the patient. The definite diagnosis relies on the histological examination of the bone concerned. It will show an association of dense, abundant and highly vascularised conjunctive tissue together with giant plurinuclear cells, without any mitosis nor any cellular atypia. The other bone diseases affecting the bones of the face will have to be sought, of course, and eliminated through the clinical and radiological examinations and, above all, by the histological examination which is the basis of the definite diagnosis. The treatment of cherubism is still a controversial issue: some authors are in favour of therapeutic abstention while others support the recourse to surgery to deal with the functional and aesthetic dimensions of the disease. In conclusion, the authors insist that the diagnosis of cherubism is apparently easy. Cherubism must be envisaged in the case of a chubby-cheeked child and a sample of pathological bone should be taken in order to ascertain the diagnosis.

[Cherubism: diagnosis and treatment in the pediatric age]. / Querubismo: diagnóstico y tratamiento en la edad pediátrica.

Cherubism is a benign bone dysplasia of childhood, exclusively involving maxillary bones and spontaneous resolving after puberty in different grades. Approximately, 280 cases have been reviewed in the literature. It is an autosomal dominant disorder in which the normal bone is replaced by cellular fibrous and immature bone, resulting in painless symmetrical enlargement of the jaws. Diagnosis is based in clinical and radiological findings, confirmed by histology. Treatment is a controversial issue, and it is recommended surgical management as conservative as possible during the rapid growth phases. An aggressive case of cherubism is reported, diagnosed and followed since early childhood until puberty, with progressive involvement of facial bones developing in a disruption of facial contours and occlusion. The patient is treated by several surgical interventions oriented to minimize the aesthetic impact of the disease being as conservative as possible. The highlights of this case are the great proportion of the lesions, the functional and emotional disturbances brought out by these lesions and the difficulty to choose the most appropriate age and form of treatment.

Querubismo: diagnóstico y tratamiento en la edad pediátrica / Cherubism: diagnosis and treatment in the pediatric age

El querubismo es una displasia ósea benigna de la infancia, que afecta exclusivamente a los huesos maxilares y se resuelve en gradovariable de forma espontánea durante la pubertad. Se han descrito aproximadamente 280 casos en la literatura, la mayoría en varones. Es una enfermedad hereditaria autosómica dominante en la que el hueso normal es sustituido por hueso fibroso e inmaduro, dando lugar a una expansión indolora simétrica de los maxilares. El diagnóstico es clínico y radiológico, confirmado por la histología. El manejo es controvertido, recomendándose una actitud quirúrgica lo más conservadora posible durante la fases de crecimiento rápido. Se presenta un caso agresivo de querubismo diagnosticado y seguido desde la infancia precoz hasta la pubertad, con afectación progresiva amplia de los huesos faciales, provocando una disrupción de los contornos de la cara y la oclusión. El paciente es tratado mediante una serie de intervenciones encaminadas aminimizar el impacto estético de la enfermedad de la forma más conservadora posible. El interés del caso se centra en la amplia extensión dela enfermedad, los trastornos funcionales y emocionales que provoca y la dificultad para elegir el momento adecuado y el tipo de intervención (AU)

Cherubism is a benign bone dysplasia of childhood, exclusively involving maxillary bones and spontaneous resolving after puberty indifferent grades. Approximately, 280 cases have been reviewed in the literature. It is an autosomal dominant disorder in which the normal bone is replaced by cellular fibrous and immature bone, resulting in painless symmetrical enlargement of the jaws. Diagnosis is based inclinical and radiological findings, confirmed by histology. Treatment is a controversial issue, and it is recommended surgical management as conservative as possible during the rapid growth phases. An aggressive case of cherubism is reported, diagnosed and followed since early childhood until puberty, with progressive involvement of facial bones developing in a disruption of facial contours and occlusion. The patient is treated by several surgical interventions oriented to minimize the aesthetic impact of the disease being as conservative as possible. The highlights of this case are the great proportion of the lesions, the functional and emotional disturbances brought out by these lesions and the difficulty to choose the most appropriate age and form of treatment (AU)

The surgical and orthodontic management of cherubism in a growing child.

Cherubism is a rare non-neoplastic disease that affects the jaws causing significant destruction and disfigurement. The disease also affects the normal eruption, occlusion and function of the dento-alveolar complex. Cherubism may radiographically and histologically resemble central giant cell granuloma, fibrous dysplasia and other giant cell lesions. The case of a 15-year 4-month-old girl with no obvious facial swelling or signs of cherubism is described in this report. The patient presented with a dental malocclusion that included the ectopic eruption and displacement of teeth caused by the lesion. The radiographic findings derived from Cone Beam Computed Tomography (CBCT) technology are described. This case report details the orthodontic and surgical diagnosis and management of a teenager during the post growth period.

Multidisciplinary surgical management of cherubism complicated by neurofibromatosis type 1.

UNLABELLED: Cherubism is a rare, autosomal dominant, mostly self-limiting disease of the jaw. It is characterized by bilateral fibrous tissue hyperplasia, giant cell proliferation, and bony degeneration in the lower facial skeleton, which can result in a massive and severely deforming prominence of the maxillomandibular structure. This case study examines the multidisciplinary management of a severe case of cherubism complicated by neurofibromatosis type 1, 2 codominant nonsegregating conditions that were clinically and genetically diagnosed, an extremely rare combination. Adequate mandibular reduction, reconstruction, and dental implantation afforded good restoration of oral function as well as a marked aesthetic improvement. METHODS: A 14-year-old Fijian girl was referred to our unit for management of severe overgrowth of her mandible that compromised her speech and deglutition. In addition, she displayed clinical features consistent with neurofibromatosis type 1. Radiologic, histologic, and genetic analyses confirmed the diagnosis of both conditions. Our craniofacial multidisciplinary team undertook mandibular reconstruction followed by placement of osseointegrated dental implants. RESULTS: Mandibular reduction, reconstruction, and dental implantation resulted in a significantly improved functional and aesthetic outcome with no further regrowth at 3-year follow-up when she returned to the United Kingdom for osseointegrated dental implant insertion. CONCLUSIONS: The successful outcome of this surgically challenging, grossly disfiguring, and rare condition was largely a result of the combined input from our multidisciplinary team, adequate preoperative planning, and the use of a novel surgical technique in debulking and reconstructing her mandible.

Postpubertal nonfamilial cherubism and teeth transposition.

Cherubism is a rare, nonneoplastic, fibro-osseous disease. It is an autosomal-dominant disorder in which the normal bone is replaced by cellular fibrous tissue and immature bone. It is genetically inherited, although many nonfamilial cases have been reported. Cherubism is a bone disease clinically characterized by bilateral, painless enlargements of the jaws. The mandible is the most severely affected craniofacial component, in which uncontrolled growth of the malady deteriorates the aesthetic balance of the face. A malocclusive and abnormal dentition, worse in the mandible, can be seen. Histopathologically, numerous randomly distributed multinucleated giant cells and vascular spaces within a fibrous connective tissue stroma with or without eosinophilic collagen perivascular cuffing were apparent. The appearance of the affected children is normal at birth. Between the ages of 2 and 7 years, swellings within the mandibular body or tuberosities of maxilla appear. This article relates to a postpubertal nonfamilial cherubism case that was noticed with multiple radiolucencies in radiographic examination and its effects on teeth.

[Cherubism]. / Le chérubisme.

Cherubism is an extensive cystic-like growth mostly affecting the mandible. It is often diagnosed because of a swollen lower half of the face in children. There are familial and de novo cases. The autosomal dominant cases are related to exon 9 -SH3BP2 mutation. The treatment is mainly surgical combining cyst curettage and modeling resections. Anti-TNF therapy could be a new treatment option.

Diagnosis and treatment of familial cherubism characterized by early onset and rapid development.

Cherubism is a benign maxillary bone dysplasia of childhood, usually showing an autosomically dominant inheritance with variable penetrance and spontaneously resolving after puberty. Only maxillary bones are affected and develop pseudocystic osteolytic lesions. This article presents an early and rapidly evolving familial case of cherubism. The 3-year-old child underwent conservative curettage of lesions, with a conservative approach that allowed a normal permanent dentition in adolescence. Family history revealed that the father had been treated for similar lesions between 14 and 21 years of age, but the late treatment caused edentulism. In conclusion, although cherubism represents a benign and localized maxillary dysplasia, it requires prompt surgical but conservative treatment and careful follow-up to avoid permanent lesions, that is, malocclusion and/or edentulism.

Oral to nasal tube exchange under fibroscopic view: a new technique for nasal intubation in a predicted difficult airway.

For a predicted difficult airway, oral intubation techniques are well established in pediatric anesthesia, but nasotracheal intubation remains a problem. There are many reports concerning this, but the risk of bleeding, added to the lack of cooperation make this procedure difficult and hazardous. We describe a modification of the nasal intubation technique in two stages. First an oral intubation and then exchanging the oral for a nasal tube, in the case of a 13-year-old boy affected by an advanced stage of cherubism. Oral intubation using a laryngeal mask technique has already been reported, but problems appear during the exchange procedure and even more when direct laryngoscopy is impossible. Fiberscopic control of the exchange, and the introduction of a Cook Exchange Catheter into the trachea through the oral tube before withdrawal, permits oxygenation of the patient and acts as a guide for oral tube reintroduction if required.