Making sense of giant cell lesions of the jaws (GCLJ): lessons learned from next-generation sequencing.

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.

Giant cell reparative granuloma of the scapula: report of a case and literature review.

Giant cell reparative granulomas (GCRGs) are non-neoplastic inflammatory lesions, usually observed in the maxilla, mandible or small bones of the hands and feet. These lesions present a wide range of morphology and the misinterpretation with other giant cell lesions can often occur. We report the case of a 47-year-old woman with GCRG in the left scapula, presenting some uncommon features: the location (scapula) and age at presentation, the lack of underlying bone disease such as Paget's disease or fibrous dysplasia, the large aggressive expansile aspect of the lesion. This was a therapeutic study, level IV (case series with no or a historical control group).

Foreign Body Reaction to Dialysis Chatheter and Peritoneal Fluid Eosinophilia in a Child on Continuous Ambulatory Peritoneal Dialysis.

Foreign body reaction is a tissue response against implanted materials. We described for the first time the eosinophilic peritonitis and foreign body giant cell reaction to dialysis catheter in a nonatopic child on continuous ambulatory peritoneal dialysis. We found tenderness, redness, and swelling without purulent discharge around the peritoneal catheter; increased eosinophil count in cloudy dialysis fluid; and blood and hyperechoic granulomatous formation appearance surrounding the peritoneal catheter on ultrasonography and foreign body giant cell reaction to dialysis catheter in pathologic examination of granulomatous lesionin in our patient. The peritoneal dialysis catheter was removed due to resistance to antibiotic and antihistamine treatments for suspected peritonitis and tunnel infection. Foreign body reaction and eosinophilic peritonitis with eosinophilic cloudy dialysis effluent can exist simultaneously. Foreign body reaction should be considered in the differential diagnosis of exit site and/or tunnel infection. Ultrasonography helps distinguish between foreign body reaction and exit-site or tunnel infection.

Combination therapies for the treatment of recurrent central giant cell lesion in the maxilla: a case report.

BACKGROUND: Central giant cell lesion is a non-neoplastic proliferation, usually asymptomatic, of unknown etiology. The purpose of this case report is to report the diagnosis and the treatment of a recurrent central giant cell lesion in the maxilla. CASE PRESENTATION: A 31-year-old Brazilian woman presented to our Surgery Service for evaluation of a cystic lesion in her teeth 13 and 15, although she had previously received endodontic treatment for her teeth 13 and 15 without regression of the lesion. On clinical examination, an increase and painless swelling was observed in her right jaw. An excisional biopsy of the lesion was performed under general anesthesia; the material was sent for pathological examination and a diagnosis compatible with central giant cell lesion was made. She presented again, 10 months after the removal of the lesion, with a recurrent lesion that surrounded her incisors, canine, and right premolar. We suggested that she underwent treatment with intralesional corticosteroids injection. The lesion was significantly reduced and the remainder of the lesion was enucleated. She is monitored at 3-month intervals; at 6 months postoperatively there has been no recurrence. CONCLUSIONS: Central giant cell lesion can have a high degree of invasiveness, which increases the importance of early diagnosis. Combination therapies can provide a favorable prognosis. Periodic monitoring is recommended, thus avoiding the chance of a relapse.

Pharmacological and surgical therapy for the central giant cell granuloma: A long-term retrospective cohort study.

PURPOSE: This is a retrospective cohort study of patients with a central giant cell granuloma (CGCG) treated at a single center to assess and compare the different surgical and non-surgical approaches. MATERIAL AND METHODS: A cohort with a single histologically proven non-syndrome-related CGCG was selected and reviewed. Patients were allocated to group I (surgery), group II (pharmacotherapy), and group III (pharmacotherapy and surgery). The primary outcome was long-term radiologic response using computed tomography. Secondary outcomes were intermediate radiologic responses and occurrence and severity of side effects. RESULTS: Thirty-three subjects were included in the study. The surgical group (n = 4) included 1 patient with progression during follow-up and a relatively high post-surgical morbidity. Twenty-nine patients started on various pharmacological treatment regimens (groups II and III). Fourteen patients could be managed without additional surgery. One of these lesions showed progression during follow-up. The other 15 lesions underwent additional surgery, and none showed progression during follow-up. Interferon treatment was associated with the most side effects. CONCLUSION: Pharmacological agents have a role in the treatment of aggressive and non-aggressive CGCGs by limiting the renewed progression during long-term follow up and the extent and morbidity of surgical treatment.

Efficacy of Ethanolamine Oleate Sclerotherapy in Treatment of Peripheral Giant Cell Granuloma.

PURPOSE: The aim of this study was to evaluate the efficacy of ethanolamine oleate (EO) sclerotherapy in the treatment of peripheral giant cell granuloma. PATIENTS AND METHODS: This study included 24 patients presenting with PGCGs greater than 2 cm in diameter. Definitive diagnosis was confirmed after histopathologic examination of incisional biopsy specimens. EO sclerotherapy at a concentration of 2.5% was injected into each lesion once a week. Repeated injections were performed if needed. The treatment response was recorded as complete remission, moderate response, or no change. RESULTS: This study involved 11 male and 13 female patients, ranging in age from 9 to 70 years; the average age was 45.3 years. The mandible (75%) was involved more than the maxilla. PGCGs occurred posteriorly (62.5%) more than anteriorly. The number of injection sessions was 57, with an average of 2.4 sessions per lesion. Clinical improvement was seen in 23 patients: complete remission in 20 (83.3%) and moderate improvement in 3 (12.5%). No clinical improvement occurred in 1 patient (4.2%). CONCLUSIONS: EO injection offers an alternative to conventional methods for the treatment of PGCG. The technique is straightforward, safe, and cost-effective with a high success rate.

Central Giant Cell Granuloma of the Mandible Requiring Multiple Treatment Modalities: A Case Report.

Central giant cell granuloma (CGCG) is a relatively rare non-neoplastic, intraosseous lesion that exhibits a wide spectrum of clinical behavior, and its management can be particularly challenging even for experienced clinicians. The etiopathogenesis of this disease process remains unclear, although factors such as trauma, inflammatory foci, and a genetic predisposition have been implicated. Although multiple treatment modalities have been used with varying degrees of success, there is no accepted algorithm for therapeutic intervention and little is known about the reasons for success or failure of a given treatment. This article reviews the epidemiology, presentation, classification, and currently used therapies for CGCG while describing the clinical course and successful therapeutic outcome of a young female patient with an aggressive CGCG of the mandible.

[Central giant cell granuloma in children: Presentation of different therapeutic options]. / Granulome central à cellules géantes de l'enfant : présentation des différentes options thérapeutiques.

Central giant cell granuloma (CGCG) is a benign tumor that may be subdivided in a non-aggressive form and an aggressive form. In aggressive forms, tumor size and high recurrence risk need large surgical resections. In order to minimize surgical morbidity, especially in children, medical treatments acting on the tumor proliferation are currently being assessed: steroids (triamcinolone), anti-osteoclastic drugs (calcitonine, alendronate, denosumab), anti-angiogenic drugs (interferon α). However to date, there is no evidence for any superiority of medical over surgical treatment. Complete response is rarely obtained and additional surgery is often necessary to remove the tumor in case of tumor progression, to remove a remnant or to remodel bone. Moreover, these drugs have frequent local or systemic side effects such as osteonecrosis and growth deficiencies.

Anogenital granulomatosis: report of two cases.

Anogenital granulomatosis (AGG) is a rare chronic inflammatory disorder of unknown aetiology. It presents clinically with swelling of the genital or anoperineal area, with histopathological findings of noncaseating giant cell granulomas. Some cases of AGG are associated with underlying systemic disease, mainly Crohn disease. We report two patients with AGG. The first was a young man with ulcerative colitiis treated with infliximab, which also alleviated the developing symptoms of AGG. The second was a young woman who was otherwise healthy. After the introduction of complex decongestive therapy, the oedema was considerably reduced in both patients.

Giant cell-rich osteosarcoma or giant cell reparative granuloma of the mandible?

Giant cell-rich osteosarcoma (GCRO) is a rare subtype of osteosarcoma, and no literature has reported occurrence in the mandible region up to now. In this article, we report a case of GCRO originating from the mandible in a 67-year-old woman who presented a history of painless mass located in the left side of the mandible after teeth extraction. The curettage biopsy histologic diagnosis is giant cell reparative granuloma before mandibulectomy surgery, but panoramic radiograph revealed an osteolytic lesion. The tumor was completely resected with segmental mandibulectomy and soft tissue with postoperative histologic diagnosis of GCRO. The free fibula osteomyocutaneous flap was performed to reconstruct the defect of the mandible and gingival mucosa. The patient received postoperative radiotherapy and chemotherapy. The 1-year follow-up situation is fine.

Orthopedic and orthodontic treatment in central giant cell granuloma treated with calcitonin.

Central giant cell granuloma of the jaw is a benign lesion of unknown etiology that occurs with very low frequency. It mainly occurs in children and young adults and is more common in the mandible. The most common treatment is surgical removal; however, alternative therapies (intralesional injections of corticosteroids, interferon alpha, and calcitonin) have been used in order to avoid undesirable damage to the jaws and teeth. The lesion may cause root resorption, tooth germ displacement, and other dental problems, as well as malocclusion that must be treated orthodontically. The orthodontic, orthopedic, and calcitonin-based treatments of one of these cases is presented.

Granuloma reparativo de células gigantes agresivo en región mandibular / Aggressive giant cells reparative granulomas in mandibular region

El granuloma reparativo de células gigantes (GRCG) es un proceso reactivo agresivo, que aparece con mayor frecuencia en los sectores anteriores de la mandíbula y el maxilar, en niños y adolecentes jóvenes. Constituye el 1 por ciento de las lesiones óseas tumorales. Existe una considerable controversia acerca de si son lesiones benignas o reactivas; también desde el punto de vista de su origen, de sus características clínicas e histológicas, así como su terapéutica. En octubre de 2007 acudió un caso a consulta externa de Cirugía Maxilofacial del Hospital Pediátrico Universitario Juan M Márquez, con una lesión diagnosticada como GRCG agresivo, la cual provocó gran deformidad facial y osteólisis del cuerpo mandibular. Se realizaron exámenes físicos, complementarios e iconopatográfico. Se ejecutó tratamiento quirúrgico y análisis de la pieza. La paciente no tuvo alteraciones estéticas ni funcionales. Hubo ausencia de recidiva, luego de 30 meses de seguimiento. Se revisó la literatura más reciente en los sitios Med Line, Lilac, Google, con las palabras clave granuloma reparativo de células gigantes, en inglés y español, para comparar nuestros procederes y resultados con otros reportes(AU)

The giant cells reparative granulomas (GCRG) is a reactive and aggressive process appearing more frequently in anterior sector of mandible and maxilla in children and young adolescents accounting for the 1 percent of tumor bone lesions. There is a considerable controversy if they are benign or reactive lesions from the point of view of its origin, from its clinical and histological features as well as therapeutical. This is the case of a patient seen in external consultation of Maxillofacial Surgery of the Juán Manuel Márquez Children and University Hospital at October, 2007 in whom an extent lesion diagnosed as an aggressive GCRG provoked a facial deformity and osteolysis of mandibular body. Complementary, physical and iconopathographic examinations were made as well as surgical treatment and analysis of this sample. Patient has neither aesthetic alterations nor functional. There was no relapse after 30 months of follow-up. We made a review of more update literature in Med Line, Lilac and Google websites with the giant cells reparative granulomas as key words in English and Spanish languages, to compare our procedures and results with other reports(AU)

Tratamiento quirúrgico de un granuloma central agresivo de células gigantes del maxilar superior / Central giant cell granuloma of maxilla: surgical treatment

Si bien es una lesión benigna, el granuloma central de células gigantes puede provocar erosión ósea y asimetría facial. Se describe el tratamiento quirúrgico exitoso de una lesión de estas características ubicada en el maxilar superior.

Interventions for central giant cell granuloma (CGCG) of the jaws.

BACKGROUND: Central giant cell granuloma (CGCG) of the jaws is a rare benign tumour with an unknown aetiology accounting for up to 7% of tumours in the mandible (lower jaw) and the maxilla (upper jaw). OBJECTIVES: This systematic review focused on assessing the effects of primary non-surgical versus primary surgical interventions or any other treatment or placebo for treating central giant cell granuloma of the jaws. SEARCH STRATEGY: Relevant randomised controlled trials (RCTs) were identified from the Cochrane Oral Health Group's Trials Register (July 2009); CENTRAL (The Cochrane Library 2009, Issue 3); MEDLINE (1950 to July 2009); EMBASE (1980 to July 2009); and LILACS (1982 to July 2009). We scanned bibliographies of relevant studies for possible references to additional trials as well as prospective clinical trial registries. Eligible RCTs were included regardless of the language of publication. SELECTION CRITERIA: Randomised controlled trials involving a comparison of primary non-surgical interventions with primary surgical interventions or any other treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility, risk of bias and extracted data. The Cochrane Collaboration statistical guidelines were followed. MAIN RESULTS: We did not find any study evaluating the effects of primary surgical versus primary non-surgical interventions for central giant cell granuloma of the jaws. However, we included and analysed one RCT with unclear risk of bias, evaluating the effects of calcitonin versus placebo for central giant cell granuloma of the jaws. No significant difference was found in the proportion of patients with increased volume of more than 10% of the lesion compared to the pretreatment measurement at 3 months of follow-up (one RCT, 14 participants; risk ratio (RR) 3.00, 95% confidence interval (CI) 0.40 to 22.30). AUTHORS' CONCLUSIONS: We did not find RCTs evaluating the effects of primary surgical versus primary non-surgical interventions for central giant cell granuloma of the jaws. Although a number of non-surgical therapies have been proposed for treating central giant cell granuloma of the jaws, our review did not identify evidence from RCTs to support their use. More research is needed on this topic.

Lesão periférica de células gigantes em mucosa palatina / Giant cell peripheral granuloma in palatinal mucosa

São conhecidas diversas lesões que apresentam particular predileção pelo periodonto. A lesão periférica de células gigantes é um processo proliferativo reacional não neoplásico, apresentando-se relativamente freqüente na clínica estomatológica, podendo atingir dimensão variada e, subseqüentemente necessidades terapêuticas particulares. O propósito deste trabalho foi relatar um caso de uma paciente que apresentou uma lesão de tamanho avançado, localizada em mucosa palatina de prémolares e molares, na qual dificultou a fonação e a deglutição. A lesão foi removida pela exérese cirúrgica e o diagnóstico foi lesão periférica de células gigantes. Foram discutidas as características clínicas e histopatológicas, incidência e freqüência, diagnóstico diferencial, etiopatogênese, modalidades de tratamento e prognóstico.

Many lesions with periodontal predilection are known. The giant cell peripheral granuloma is a reaction proliferative process, non neoplasic, that is relatively frequent in stomatologic clinic, can arrive variable size and, subsequently, needs particulary therapeutic. The purpose of this work is to report a patient case that show an advanced size lesion, localized in palatine mucous of molar and premolar teeth that complicated deglutition and phonation. The lesion was removed by surgical excision and the diagnosis was giant cell peripheral granuloma. Clinical and histopatological characteristics, incidence and frequency, differential diagnosis, etiopathogenesis, therapeutic modalities and follow-up were discussed.