Gorham-Stout Disease Research Articles

Gorham-Stout disease with parietal bone osteolysis: a case series and review of literature

Background Gorham-Stout disease (GSD) is a rare and idiopathic bone disorder, characterized by massive osteolysis. To date, there is no established treatment strategy for GSD. We empirically treated two patients, who had presented to us with cranial lesions of GSD. Here, we propose a novel algorithm for the management of Gorham’s disease based on our experience and review the literature published to date. Methods We reviewed all existing literature on GSD describing the pathophysiology and suggested treatment methods, up to 2018. Results We found 13 papers with 14 reported cases; an inclusion of our two cases brings the total count up to just 16 recorded cases of GSD involving the skull. Of these, the base of the skull was affected in eight cases, while the remaining eight cases showed cranial involvement. The patients with skull-base involvement were managed conservatively, using medications or radiotherapy. The patients with cranial osteolysis were managed surgically, with an excision of the osteolytic portion, followed by cranioplasty. Of the latter group, the pericranium was not removed in one patient, in whom a very slight progression of the osteolytic process was later observed. Conclusions The pathogenesis of GSD remains poorly understood. Further study is required to determine an optimum management strategy. A long-term follow-up will also be necessary to establish the effectiveness of the treatment process. The untreated patients show a progressive resorption of the affected bones of the skull. A painful, vanishing skull deformity is an alarming sign of GSD. Early diagnosis and treatment are necessary to arrest disease progression and to prevent complications.

Gorham–Stout disease: good results of bisphosphonate treatment in 6 of 7 patients

Background and purpose — Gorham–Stout disease (GSD) is a rare mono- or polyostotic condition characterized by idiopathic intraosseous proliferation of angiomatous structures resulting in progressive destruction and resorption of bone. Little is known about the course of disease and no previous study has evaluated patients’ quality of life (QoL).Patients and methods — This is a retrospective analysis of 7 consecutive patients (5 males) with a median age at diagnosis of 14 years and a median follow-up of 7 years who were diagnosed with GSD in our department between 1995 and 2018. Data regarding clinical, radiographic, and histopathological features, and treatment, as well as sequelae and their subsequent therapy, were obtained. QoL was assessed by Musculoskeletal Tumor Society Score (MSTS), Toronto Extremity Salvage Score (TESS), and Reintegration to Normal Living (RNL) Index.Results — 3 patients had a monoostotic and 4 patients a polyostotic disease. Besides a diagnostic biopsy, 4 of the 7 patients had to undergo 8 surgeries to treat evolving sequelae. Using an off-label therapy with bisphosphonates in 6 patients, a stable disease state was achieved in 5 patients after a median of 20 months. The median MSTS, TESS, and RNL Index at last follow-up was between 87% and 79%.Interpretation — Due to its rare occurrence, diagnosis and treatment of GSD remain challenging. Off-label treatment with bisphosphonates appears to lead to a stable disease state in the majority of patients. QoL varies depending on the individual manifestations but good to excellent results can be achieved even in complex polyostotic cases with a history of possibly life-threatening sequelae.

Ectopic teeth in a patient with Gorham-Stout disease previously treated by biphosphonates: a case report

Introduction: Gorham-Stout disease is a rare idiopathic condition of the bone that is characterized by a massive and spontaneous osteolysis, with a vascular or lymphatic proliferation in bone, which is then replaced by fibrous tissue. Observation: a 16-year-old patient was referred to the maxillofacial surgery department to remove ectopic teeth bilaterally in the ramus. He had Gorham-Stout disease, managed for many years in orthopedic surgery department for a lower limb lesion and in neurosurgery department for a breach of the meninges. He was treated for 4 years with bisphosphonates. The removal of the ectopic teeth went well, with a simple postoperative course. Discussion: Gorham-Stout disease physiopathology remains unknown. Facial bones are often involved, especially the mandible. There are many possible treatments, but, due to the rarity of the disease, no therapeutic consensus exists. Bisphosphonates seem to be a good way to control this condition. So far, no case of bisphosphonates related osteonecrosis of the jaw has been reported in children. Conclusion: Gorham-Stout disease can involve the mandible and may lead to ectopic teeth.

Lymphatics in bone arise from pre-existing lymphatics.

Bones do not normally have lymphatics. However, individuals with generalized lymphatic anomaly (GLA) or Gorham-Stout disease (GSD) develop ectopic lymphatics in bone. Despite growing interest in the development of tissue-specific lymphatics, the cellular origin of bone lymphatic endothelial cells (bLECs) is not known and the development of bone lymphatics has not been fully characterized. Here, we describe the development of bone lymphatics in mouse models of GLA and GSD. Through lineage-tracing experiments, we show that bLECs arise from pre-existing Prox1-positive LECs. We show that bone lymphatics develop in a stepwise manner where regional lymphatics grow, breach the periosteum and then invade bone. We also show that the development of bone lymphatics is impaired in mice that lack osteoclasts. Last, we show that rapamycin can suppress the growth of bone lymphatics in our models of GLA and GSD. In summary, we show that bLECs can arise from pre-existing LECs and that rapamycin can prevent the growth of bone lymphatics.

Gorham-Stout Disease of the Shoulder: Clinical, Pathologic and Therapeutic Considerations.

Gorham-Stout disease (GSD) is a rare skeletal disorder characterized by massive osteolysis of a bony area in the body. When it hits the shoulder, the patient is faced with a debilitating limitation in terms of motion, stability and quality of life. GSD etiology and pathology are unknown and, as a result, therapeutic modalities remain unclear. The aim of this paper is to explore and offer medical insight into the possible etiologies, pathologies and therapeutic modalities of GSD in the shoulder. We explored PubMed/Medline for GSD cases in the shoulder. The search involved all articles published from database inception until February 1, 2019. Only articles published in English were included. Demographics and clinical information extrapolated from the reported cases were analyzed to deduce patterns and infer conclusions. Only 32 studies met our criteria, with a total of 37 cases (n=37). Males predominated in 21 cases (57%). Twelve cases (32%) were younger than 18 years, and 18 cases (49%) were aged between 18 and 65 years. Shoulder pain was the predominant reporting symptom. The humerus was the most common shoulder site affected (54%), followed by the scapula (35%) and the clavicle (30%). Almost half of the cases affected the right shoulder (51%), the left shoulder was affected in 16 cases (43%). Conservative treatment was opted in 17 cases (46%), while surgery was performed in 13 cases (35%). Good outcomes were reported in 28 cases (76%), while death occurred twice (5%). Understanding the demographics and clinical characteristics of GSD in the shoulder region will help in formulating better therapeutic interventions and preventive health policies.

A case report of Gorham-Stout disease diagnosed during the course of recurrent meningitis and cholesteatoma

BackgroundGorham-Stout disease is a rare bone disorder. Here, we present a case of Gorham-Stout disease diagnosed during follow-up of a patient with cholesteatoma; the disease affected the temporal bone and other sites of the skull. To the best of our knowledge, this is the first report of Gorham-Stout disease diagnosed with recurrent cerebrospinal leakage after surgery to treat cholesteatoma.Case presentationA 25-year-old male patient re-presented to our department for the first time in 7 years with otorrhea in the right ear and recurrent meningitis. The patient had a history of multiple surgeries for cholesteatoma and suffered from recurrent cerebrospinal fluid leakage, which initially was thought to be caused by recurrence of cholesteatoma. Therefore, skull base reconstruction was planned. However, the underlying cause was identified eventually as defects in the temporal bone caused by massive osteolysis due to Gorham-Stout disease. Skull base reconstruction was abandoned because the osteolysis was considered to be progressive. Conservative treatment with infectious control was implemented as an alternative.ConclusionThis case describes unusual temporal bone osteolysis after cholesteatoma surgery and the importance of considering the possibility of multiple concurrent diseases in such individuals. The distinguishing features of this case are the fact that the temporal bone had disappeared, and deconstruction was complicated by infection and inflammation caused by cholesteatoma, surgical invasion, and Gorham-Stout disease. Appropriate diagnosis saved the patient from ineffective multiple surgeries for cerebrospinal fluid leakage or cholesteatoma, and improved his quality of life.

Gorham-Stout disease of the malleolus: a rare case report

BackgroundGorham-Stout disease, also known as vanishing bone disease, idiopathic massive osteolysis, is a rare entity of unknown etiopathology. This disease is characterized by destruction of osseous matrix and proliferation of lymphatic vascular structures and associated with massive regional osteolysis. It has a variable clinical presentation and is commonly considered as a benign disease with a progressive tendency and an unpredictable prognosis. The diagnosis is made by exclusion and based on combination with histological, radiological, and clinical features. Despite that several therapeutic options have shown certain efficacy, the effective treatment still remains controversial and there is no standard treatment to be recommended.Case presentationA previously healthy 40-year-old man presented with right lateral malleolus pain after an ankle sprain and was referred to our hospital. The radiographs indicated rapid massive bone destruction in the distal right lateral malleolus with an unclear margin. Based on the combination with histological, radiological, and clinical features, the diagnosis of Gorham-Stout disease was made. Considering that the residual function of malleolus had to be protected, prior bisphosphonate was used to control the progression of lesion, followed by surgical resection and biological reconstruction with autologous fibular bone grafting. The patient was followed up 8 years after surgery, he presented without progression and recurrence.ConclusionsWe depict a case of Gorham-Stout disease at the right lateral malleolus and was successfully controlled by medication and surgical intervention. Based on the prior effective medical treatment, resection with biological reconstruction is a useful approach to treat Graham-Stout disease in bone.

Gorham-Stout disease in the rib and thoracic spine with spinal injury treated with radiotherapy, zoledronic acid, vitamin D, and propranolol: A case report and literature review.

Gorham-Stout disease (GSD) is a rare bone condition that is characterized by the spontaneous, idiopathic and progressive proliferation of blood or lymphatic vessels, which replace the bone and marrow space. The precise etiology and pathophysiology of GSD remain poorly understood. Therefore, there is no consensus on the treatment of this disease. In the current study, a rare case of GSD in the rib and thoracic spine with spinal injury that was treated with radiotherapy, zoledronic acid, vitamin D and propranolol, is reported. A 77-year-old man visited the hospital complaining of constipation for 10 days. Within a few days, the patient had recognized complete paralysis of the bilateral lower legs. Radiologically, large osteolytic lesions were confirmed in the 6, 7 and 8th right ribs, the 6 and 7th thoracic vertebrae and in the liver and spleen. The lesions were diagnosed as GSD based on clinical findings, imaging characteristics and needle biopsy results. The patient was treated with zoledronic acid, activated vitamin D, propranolol and radiotherapy to the thoracic vertebrae. However, approximately 5 months after the first treatment, the rapidly increasing hemorrhagic pleural effusion compressed the left lung and caused a mediastinal shift to the right thorax. Unfortunately, the patient succumbed to the disease 7 months after first admission. To the best of our knowledge, this is the first reported case of GSD in the rib and thoracic spine with spinal injury to be treated with radiotherapy, propranolol, vitamin D and zoledronic acid. Furthermore, there have been no previous reports of a mediastinal shift caused by intralesional hemorrhage in GSD. For future reference, it should be noted that such processes may occur in GSD lesions of the thoracic spine and/or thorax. The present case will therefore contribute to a deeper understanding of GSD, a rare clinical entity.

Dissecting the mechanisms of bone loss in Gorham-Stout disease.

Gorham-Stout disease (GSD) is a rare disorder characterized by progressive osteolysis and angiomatous proliferation. Since the mechanisms leading to bone loss in GSD are not completely understood, we performed histological, serum, cellular and molecular analyses of 7 patients. Increased vessels, osteoclast number and osteocyte lacunar area were revealed in patients' bone biopsies. Biochemical analysis of sera showed high levels of ICTP, Sclerostin, VEGF-A and IL-6. In vitro experiments revealed increased osteoclast differentiation and activity, and impaired mineralization ability of osteoblasts. To evaluate the involvement of systemic factors in GSD, control cells were treated with patients' sera and displayed an increase of osteoclastogenesis, bone resorption activity and a reduction of osteoblast function. Interestingly, GSD sera stimulated the vessel formation by endothelial cells EA.hy926. These results suggest that bone cell autonomous alterations with the cooperation of systemic factors are involved in massive bone loss and angiomatous proliferation observed in GSD patients.

Management of a pathological fracture in a rare case of Gorham Stout disease of the hip with a mega prosthesis

Gorham-Stout disease (GSD) is a rare bone disease of unknown etiology, characterized by spontaneous and progressive resorption of bones. This disease occurs most commonly in males of the age group of fewer than 40 years and has no genetic predisposition. It most commonly affects the skull, spine, pelvis and shoulder girdle. The diagnosis of GSD is established based on the combination of clinical, radiologic, and histological features, after excluding other diseases. There is no standard treatment for it so far, and the therapy depends on patient's clinical condition and may include surgery, radiotherapy, and drugs, with varying degrees of success. To the best of our knowledge such involvement of hip and its treatment by a megaprosthesis, in an elderly lady by GSD has not been reported. This case report describes an unusual presentation of the disease of the hip in an elderly female successfully treated with replacement of the deficient proximal femur by using a bipolar hip mega prosthesis of the hip (XLO, India).

A report of two children with Gorham-Stout disease

BackgroundGorham-Stout disease is a rare condition characterized by unifocal and massive type IV osteolysis (variant of idiopathic nonhereditary osteolytic disease) with a slow progression, which is self-limiting for some years. It is characterized by recurrent vascular tumors with disruption of the anatomical architecture and intraosseous proliferation of vascular channels that leads to the destruction and resorption of the bone matrix. The aim of this study is to present the clinical features of this disease, as well as the importance of prompt diagnosis and treatment, with a review of the reported cases.Case reportsWe describe two cases of Gorham-Stout disease between 2013 and 2017 with surgical interventions, follow-up and results. Case one involves an 11-year-old male with involvement of the left iliac bone, with adequate evolution after a surgical procedure with a lyophilized cadaveric tricortical bone allograft. Case two involves a 6-year-old male with cervical spine C1-C3 repercussion; in the protocol for surgical treatment, he presented with signs of spinal cord compression and died.ConclusionDiagnosis of Gorham-Stout disease is made by exclusion, and its clinical presentation varies widely, from spontaneous remission to a fatal outcome.

The impact of sirolimus therapy on lesion size, clinical symptoms, and quality of life of patients with lymphatic anomalies

BackgroundLymphatic anomalies (LAs) include several disorders in which abnormal lymphatic tissue invades the neck, chest, and various organs. Progressive cases may result in lethal outcomes and have proven difficult to treat. Sirolimus is showing promising results in the management of vascular anomalies. We examined the efficacy and safety of sirolimus treatment in patients with progressive LAs.MethodsAll patients with LAs treated with sirolimus from May 2015 to September 2018 were included. They received oral sirolimus once a day and the dose was adjusted so that the trough concentration remained within 5–15 ng/mL. We prospectively reviewed the response to drugs (the response rate of radiological volumetric change of the target lesion), severity scores, reported quality of life (QOL), and adverse effects at 6 months after administration.ResultsTwenty patients (five with cystic lymphatic malformation (LM), three with kaposiform lymphangiomatosis, three with generalized lymphatic anomaly, six with Gorham-Stout disease, and three with central conducting lymphatic anomaly) were treated with sirolimus at our institution. Fifty percent of patients (10/20) demonstrated a partial response by a radiological examination and a significant improvement in disease severity and QOL scores (P = 0.0020 and P = 0.0117, respectively). Ten patients who had no reduction in lesion size (stable disease group) showed no significant improvement in disease severity and QOL scores. Eighty percent of patients (16/20) had side effects, such as stomatitis, infection, and hyperlipidemia.ConclusionsSirolimus impacts the reduction of the lymphatic tissue volume of LMs and could lead to improvement in clinical symptoms and QOL.Trial registrationUMIN Clinical Trials Registry, UMIN000016580. Registered 19 February 2015,

Management of Gorham Stout disease with skull-base defects: Case series of six children and literature review

BackgroundGorham-Stout disease (GSD) is a rare lymphatic disorder which results in bone destruction. Defects of the skull base are difficult to manage, we describe cases to better understand the disease and discuss treatment. MethodsRetrospective study including all patients treated for GSD skull-base defects. Medical records, clinical, imaging and treatment data were studied. A systematic review of the literature included case reports of the diseases for further analysis. Results6 patients (5 males, 1 female) were included. Mean age at diagnosis was 3.5 years (range 0–10). Follow-up was of 5.2 years. Patients were divided into Naso-temporal (NT) and Vertebro-temporal (VT) groups following anatomical location. NT patients (4 patients) all had petrous defects extending anteriorly, including sphenoid, ethmoidal and mandibular defects. They all had cerebro-spinal fluid leak (CSF) and recurrent meningitis (range from 3 to 7). Two of those patients had sequelae including deafness, paralysis and epilepsy. VT patients (2 patients) all had temporal, occipital bone and cervical vertebrae defects. None had CSF leaks but both died from medullar compression (preceded by tetraparesis in one case). Overall, five out of six patients had type I Chiari malformation. Interferon seemed to be the most efficient medical treatment. Surgery included petrectomy, endonasal surgery for CSF leak management and neurosurgery for medullar management but could not guarantee long-term effects. ConclusionMain issues in skull base defects are CSF leaks and medullar compressions. Surgical treatment is necessary in both cases but can only be satisfactory if general medical treatment can stabilise the disease.

Generalized Lymphatic Anomaly and Gorham-Stout Disease: Overview and Recent Insights.

Significance: Generalized lymphatic anomaly and Gorham–Stout disease are extremely rare diseases with severe symptoms and poor prognosis. The etiology and clinical presentation of the patients remain poorly defined, but recent research has attempted to determine the pathogenesis of these diseases.Recent Advances: In recent years, the characteristics of complex lymphatic anomalies have been revealed. Kaposiform lymphangiomatosis is recognized as a new entity that has an aggressive course and poor prognosis. Genetic analysis revealed somatic mutations in genes associated with the phosphoinositide 3-kinase (PI3K) pathway in lymphatic malformation lesions. Somatic NRAS mutation in lymphatic endothelium from a generalized lymphatic anomaly patient was also detected as a potential cause of disease. Furthermore, studies demonstrated the efficacy of the mammalian target of rapamycin (mTOR) inhibitor sirolimus for these lymphatic diseases.Critical Issues: These diseases have overlapping symptoms, imaging features, and complications, leading to difficulty in their differential diagnosis. In addition, there are no standard therapies. Therefore, we need to determine the differences among these diseases to not only diagnose but also treat them appropriately.Future Directions: Further investigations should reveal differences in the clinical features and findings of radiological, pathological, and genetic examinations to manage each disease appropriately. Somatic mutation in genes encoding RAS/PI3K/mTOR signaling pathway components could be associated with the pathogenesis of these diseases and may be novel targets for drug therapies.

Gorham-Stout disease with thoracic, vertebral and pleural involvement: case report and literature review

Gorham-Stout disease with thoracic, vertebral and pleural involvement: case report and literature review

MON-517 Treatment of Gorham-Stout Disease with Combination Sirolimus and Denosumab

Background: Gorham-Stout Disease (GSD), or vanishing bone disease, is a rare condition characterized by lymphatic vessel proliferation associated with progressive, sometimes massive bone resorption. The underlying mechanism of osteolysis in this condition remains unclear; prevailing theories suggest that the disease is driven by lymphovascular growth factors, increased osteoclastic activity, and absence of osteoblast repair. Clinical Case: A 44-year-old Caucasian male was found to have an absent right scapula and multiple right rib fractures on an x-ray performed to evaluate chest discomfort. Notably, 3 years prior, a right shoulder MRI showed normal anatomy. He has no family history of bone disease. Physical exam showed soft tissue swelling in the area of the right scapula and limited range of motion of the right arm to 60 degrees in all directions. Serum calcium, phosphorous, and iPTH were normal. Bone resorption marker C-Telopeptide (CTx) was elevated to 722 pg/mL (93-630 pg/mL) while bone formation marker Procollagen I intact N-terminal (P1NP) was within normal limits. CT and MRI confirmed the absence of the body of his right scapula and identified posterior right rib lesions with overlying fractures. The remnant scapula and rib foci showed abnormally elevated activity on 18F-sodium fluoride (18F-NaF) PET/CT scan. Given his clinical and imaging findings, he was diagnosed with GSD. Treatment included two years of monthly denosumab (120 mg) and sirolimus (trough goal 7-13 mcg/L), followed by zoledronic acid infusion every 2 months for 3 doses to prevent the rebound bone resorption associated with denosumab cessation. After therapy, CTx was suppressed to 70 pg/mL and P1NP to 15 mcg/L (22-87 mcg/L). Serial imaging showed one new posterior right rib lesion noted after 6 months of treatment, but no further bone loss. He noted no pain or new weakness. Adverse events included worsening hypertriglyceridemia due to sirolimus as well as denosumab-induced hypocalcemia and hypophosphatemia. Discussion: There is no consensus on the optimal treatment of GSD. Medical therapy usually includes an antiproliferative agent (usually sirolimus or interferon 2b) and an antiresorptive agent (usually a bisphosphonate). The RANK-ligand inhibitor denosumab, the most potent osteoclast inhibitor, may be a more effective agent in preventing bone resorption in GSD. This case demonstrates the effective use of sirolimus and denosumab in GSD, but further study and careful monitoring for mineral metabolism side effects and rebound are needed.

Efficacy and safety of sirolimus treatment for intractable lymphatic anomalies: A study protocol for an open-label, single-arm, multicenter, prospective study (SILA).

IntroductionLymphatic anomalies (LAs) refer to a group of diseases involving systemic dysplasia of lymphatic vessels. These lesions are classified as cystic lymphatic malformation (macrocystic, microcystic or mixed), generalized lymphatic anomaly, and Gorham–Stout disease. LAs occur mainly in childhood, and present with various symptoms including chronic airway problems, recurrent infection, and organ disorders. Individuals with LAs often experience progressively worsening symptoms with a deteriorating quality of life. Although limited treatment options are available, their efficacy has not been validated in prospective clinical trials, and are usually based on case reports. Thus, there are no validated standards of care for these patients because of the lack of prospective clinical trials.MethodsThis open-label, single-arm, multicenter, prospective study will assess the efficacy and safety of a mammalian target of the rapamycin inhibitor sirolimus in the treatment of intractable LAs. Participants will receive oral sirolimus once a day for 52 weeks. The dose is adjusted so that the nadir concentration remains within 5–15 ng/ml. The primary endpoint is the response rate of radiological volumetric change of the target lesion confirmed by central review at 52 weeks after treatment. The secondary endpoints are the response rates at 12 and 24 weeks, respiratory function, pleural effusion, ascites, blood coagulation parameters, bleeding, pain, quality of life, activities of daily living, adverse events, side effects, laboratory examinations, vital signs, and pharmacokinetic data.ResultsThis is among the first multicenter studies to evaluate sirolimus treatment for intractable LAs, and few studies to date have focused on the standard assessment of the efficacy for LAs treatment. Our protocol uses novel, uncomplicated methods for radiological assessment, with reference to the results of our previous retrospective survey and historical control data from the literature.ConclusionsWe propose a multicenter study to investigate the efficacy and safety of sirolimus for intractable LAs (SILA study; trial registration UMIN000028905). Our results will provide pivotal data to support the approval of sirolimus for the treatment of intractable LAs.

Management of Gorham–Stout disease presenting as intractable pleural effusion in an adolescent: A case report and review of literature

Gorham–Stout disease (GSD) is a very rare disorder of unknown etiology, characterized by the abnormal proliferation of lymphatic endothelial cells, and also called “vanishing bone disease,” “phantom bone disease,” and “massive osteolysis,” as osteolysis is a characteristic feature. Patients present with a variety of symptoms such as swelling, pain, physical disability and deformity, shortness of breath, and neurological symptoms. It is a progressive disease, and owing to its rarity, the research and treatment options are limited. Our patient is a 15-year-old male, who presented with large mass over abdomen and chest, chylothorax, and osteolysis. This patient was initially treated with chest drains, subcutaneous drains, and sclerotherapy. Eventually, symptoms were worsened. After literature search, the patient was diagnosed with GSD, and sirolimus therapy was started. After 2 months of sirolimus therapy, the lesions subsided and well controlled.

Double whammy: A rare disorder complicating a common infection – A case report and review of literature

Gorham-stout disease (gsd), is a rare disorder of unknown etiology. although a non-malignant, non-infectious condition, gsd results in massive destruction of bones by osteolysis secondary to proliferation of blood vessels. we present a young man afflicted with this condition with coexisting tuberculous pleural effusion and the successful outcome with treatment.

Perspectives dans la maladie de Gorham–Stout

The Gorham–Stout disease belongs to lymphatic abnormalities and corresponds to a lymphatic endothelial cell proliferation under the stimulation of growth factors. This proliferation leads to a bone invasion and progressively to a typical vanishing bone aspect. Fracture risk and its consequences, chylothorax with sometimes fatal issue are the main complications of this disease. Physiopathological mechanisms remain poorly understood. Treatments of this rare bone disease, susceptible to affect every age from infant to adults, rely on bisphosphonates, radiotherapy, surgery, interferon alpha 2b and anti-angiogenic drugs such as sunitinib.