Gorham-Stout Disease Research Articles

Gorham–Stout disease of the proximal fibula treated with radiotherapy and zoledronic acid

Gorham–Stout disease is a rare disease characterized by anarchic lymphovascular proliferation causing resorption of bone sometimes leading to disastrous complications. Bone tissue is progressively replaced by angiomatic and lymphangiomatic tissue and finally by fibrous tissue. This disease is known to be ubiquitous and of complex etiology.We present a case of Gorham–Stout disease of the proximal fibula invading the proximal tibia and soft tissues of the popliteal space that was successfully treated with radiotherapy and zoledronic acid.

A case of Gorham-Stout disease with progressive cutaneous involvement

A case of Gorham-Stout disease with progressive cutaneous involvement

Thoracic osteotomy for Gorham-Stout disease of the spine: a case report and literature review.

Gorham-Stout syndrome is an aggressive, non-heritable skeletal disease characterized by osteolysis following minor trauma. The primary involvement of the spine is less common (10%) and has been described in only about 20 cases; there is no consensus about the best way to treat this condition. To report a case of Gorham-Stout syndrome involving the thoracic spine and to review the literature to suggest a post-operative treatment to prevent osteolysis. A thirty-year-old female patient was admitted to the unit in March 2013 for a pathologic T4 fracture. X-rays and CT scan revealed the onset of T4 osteolysis and an increase in thoracic kyphosis (the local kyphosis was up to 100°). We performed surgery by posterior approach, combining posterior fixation with screws and rods from T3 to T9, decompression and vertebral osteotomy of 65°. The immediate outcome of surgery was good and the patient returned home after 24days. At 6 and 12months of follow-up, the patient was walking normally with no neurological sequelae. We report a case of Gorham-Stout syndrome involving the thoracic spine that was successfully treated by interpedicular osteotomy associated with a 6month follow-up. We suggest that this strategy can provide good results, because after fusion, the disease process remains stable. Because of the lack of cases reported, surgeons must be careful when using multiple treatments, because these treatments have many side effects. Level IV case report.

Cerebrospinal fluid leakage in Gorham-Stout disease due to dura mater involvement after progression of an osteolytic lesion in the thoracic spine

Patients with Gorham-Stout disease (GSD), a rare disease of poorly understood etiopathophysiology, suffer from progressive osteolysis. Destruction of bone matrix is caused by lymphatic vessels, which can lead to CSF leakage if parts of bony structures adjacent to CSF spaces are involved. So far, fewer than 200 patients have been reported in the literature; only 4 of these patients presented with CSF leakage. The authors report the case of a 30-year-old man with GSD and CSF leakage due to dura mater involvement after progression of an osteolytic lesion in the thoracic spine. Neurosurgical intervention, including dura repair, was needed. Experimental medical therapy with rapamycin was started, leading to disease control for more than 12 months. Progression of GSD can lead to destruction of the meninges, causing CSF leakage. The authors review 4 other cases reported in the literature and discuss therapeutic options.

Gorham-Stout disease: radiological, histological, and clinical features of 12 cases and review of literature.

Gorham-Stout disease (GSD) is an exceedingly rare disease characterized by progressive osteolysis and angiomatosis. We investigate the features of this disease and evaluate the effects of bisphosphonates (BPs) on it. The clinical, radiological, and pathological characteristics of 12 patients diagnosed with GSD were summarized. Immunohistochemical staining with specific lymphatic endothelial markers (D2-40), vascular markers (CD 31, CD 34), and vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 3 (VEGFR-3) was performed in specimens of bone biopsy. Patients were treated with either BPs or conjunction therapy of radiation and BPs. The effects of BPs were evaluated by the change of radiological progression, bone mineral density (BMD) and bone turnover biomarkers. To further evaluate the prognosis, a literature review was done. Idiopathic massive osteolysis was found in all patients, including 11 polyostotic and one mono-ostotic osteolysis. Soft tissue lymphangioma was presented in four patents. Four patients were complicated with chylothorax. Endothelial cells lining the proliferative vessels were positive for CD31 and CD34 and D2-40. Mild expression of VEGF and VEGFR-3 was also revealed. Stabilization in osteolysis and improvement in BMD were observed after single therapy with BPs or combined with radiotherapy. High mortality rate was found in patients with chylothorax. Spontaneous, progressive osteolysis is the most typical sign of GSD. BPs and radiotherapy can contribute to the clinical stabilization in bone lesion of GSD. The complicated chylothorax possibly indicates poor prognosis.

Laboratory models for the investigation of lymphangiomatosis

Lymphangiomatosis is an uncommon proliferative disorder of the lymphatic vasculature whose etiology remains poorly understood. The lymphangiomatosis spectrum encompasses a remarkable heterogeneity in its potential presentation, including micro- and macrocystic isolated lymphatic malformations, thoracic and intraabdominal diffuse lymphangiomatosis, and osseous and soft-tissue presentations known as Gorham–Stout disease. Recent therapeutic advances are empirical in nature or, at best, inferential, reflecting the scanty availability of laboratory-based model systems for the mechanistic study of this disease. Several promising model systems are reviewed here. The laboratory investigation of lymphangiomatosis will likely continue to benefit from the remarkable growth of insights into the mechanisms of lymphangiogenesis and vascular development.

Complex lymphatic anomalies

Complex lymphatic anomalies include several diagnoses with overlapping patterns of clinical symptoms, anatomic location, imaging features, hematologic alterations, and complications. Lymphatic malformations likely arise through anomalous embryogenesis of the lymphatic system. Analysis of clinical, imaging, histologic, and hematologic features is often needed to reach a diagnosis. Aspiration of fluid collections can readily define fluid as chylous or not. The presence of chyle indicates dysfunction at the mesenteric or retroperitoneal level or above the cisterna chyli due to reflux. The imaging patterns of generalized lymphatic anomaly (GLA) and Gorham–Stout disease have been segregated with distinctive bone lesions and peri-osseous features. More aggressive histology (spindled lymphatic endothelial cells), clinical progression, hemorrhage, or moderate hematologic changes should raise suspicion for kaposiform lymphangiomatosis. Biopsy may be needed for diagnosis, though avoidance of rib biopsy is advised to prevent iatrogenic chronic pleural effusion. Lymphangiography can visualize the anatomy and function of the lymphatic system and may identify dysfunction of the thoracic duct in central conducting lymphatic anomalies. Local control and symptom relief are targeted by resection, laser therapy, and sclerotherapy. Emerging data suggest a role for medical therapies for complications of complex lymphatic anomalies. Outcomes include recurrent effusion, infection, pain, fracture, mortality, and rarely, malignancy. Complex lymphatic anomalies present significant diagnostic and therapeutic challenges. Results from a phase 2 study of sirolimus in these and other conditions are expected in 2014. Improved characterization of natural history, predictors of poor outcomes, responses to therapy, and further clinical trials are needed for complex lymphatic anomalies.

Gorham-Stout Disease Mimicking Spondyloarthritis

Gorham-Stout disease (GSD) is a rare disorder characterized by the proliferation of non-neoplastic thin-walled vascular tissue associated with progressive osteolysis1. A 37-year-old woman with a 7-year history of chronic bilateral pelvic pain was evaluated for aggravated left hip pain. She was diagnosed with spondyloarthritis (SpA) 4 years prior and was receiving medical treatment. Laboratory analyses were normal. Radiography and computed tomography (CT) of the pelvis showed widening of both …

Vascular Malformations and Associated Syndromes: The Role of the Orthopaedic Surgeon.

Vascular anomalies are among the most common congenital abnormalities in infants and children. The management of vascular anomalies requires interdisciplinary care and collaboration between orthopaedic surgeons, general surgeons, plastic surgeons, interventional radiologists, dermatologists, oncologists, and child life specialists, leading to the establishment of vascular anomaly teams at tertiary centers. Vascular anomalies are a heterogeneous group of conditions, with similar clinical appearance but substantially different manifestations. The development of an appropriate classification system has helped to reduce confusion regarding terminology, thus improving diagnosis and management. There are two groups of vascular anomalies: (1) vascular tumors and (2) vascular malformations. Differentiating between these two types, and their subtypes, is essential because of their distinct natural history and treatment1. The goal of this review is to highlight the role of the orthopaedic surgeon in the approach and treatment of extremity vascular malformations and to discuss diagnostic strategies and management at a multidisciplinary level. We also review the most common associated syndromes seen in the orthopaedic practice, including Klippel-Trenaunay syndrome, Proteus syndrome, Maffucci syndrome, Gorham-Stout disease or syndrome, Parkes Weber syndrome, and Bannayan-Riley-Ruvalcaba syndrome. In 1863, Virchow was the first to classify vascular anomalies into groups on the basis of their histopathologic appearance2. However, this nomenclature was confusing and often led to misdiagnosis with consequent inappropriate treatment. Mulliken and Glowacki proposed a classification system based on biological behavior …

Rare Bone Diseases and Their Dental, Oral, and Craniofacial Manifestations

Hereditary diseases affecting the skeleton are heterogeneous in etiology and severity. Though many of these conditions are individually rare, the total number of people affected is great. These disorders often include dental-oral-craniofacial (DOC) manifestations, but the combination of the rarity and lack of in-depth reporting often limit our understanding and ability to diagnose and treat affected individuals. In this review, we focus on dental, oral, and craniofacial manifestations of rare bone diseases. Discussed are defects in 4 key physiologic processes in bone/tooth formation that serve as models for the understanding of other diseases in the skeleton and DOC complex: progenitor cell differentiation (fibrous dysplasia), extracellular matrix production (osteogenesis imperfecta), mineralization (familial tumoral calcinosis/hyperostosis hyperphosphatemia syndrome, hypophosphatemic rickets, and hypophosphatasia), and bone resorption (Gorham-Stout disease). For each condition, we highlight causative mutations (when known), etiopathology in the skeleton and DOC complex, and treatments. By understanding how these 4 foci are subverted to cause disease, we aim to improve the identification of genetic, molecular, and/or biologic causes, diagnoses, and treatment of these and other rare bone conditions that may share underlying mechanisms of disease.

Vanishing Mandible: Gorhamstout the Culprit

Gorham's stout disease is rare skeletal condition presenting with massive osteolysis of the involved bone due to intraosseous vasculolymphatic tissue. This entity is rather misdiagnosed as aggressive lytic lesion, which results in patient being subjected to painful biopsy procedures. However this entity is seen to progress rapidly after any form of traumatic procedures according to some literature. Trauma is one of the important events that precedes this condition, However few cases had no antecedent trauma and were considered idiopathic. We report a 19 year old male who presented with left sided facial swelling with no antecedent trauma. Clinical features were not directive to any specific diagnosis. Various laboratory and radiological investigations were performed. Imaging was rather nonspecific other than mandibular osteolysis with no periosteal reaction or soft tissue calcification, but our experience with previous such entity, negative laboratory findings &retrospectiveclinical correlation, helped us diagnose this entity. Imaging was followed by biopsy (on clinicians demand), which confirmed our interpretation of facioskeletalgorham's.

Molecular, phenotypic aspects and therapeutic horizons of rare genetic bone disorders.

A rare disease afflicts less than 200,000 individuals, according to the National Organization for Rare Diseases (NORD) of the United States. Over 6,000 rare disorders affect approximately 1 in 10 Americans. Rare genetic bone disorders remain the major causes of disability in US patients. These rare bone disorders also represent a therapeutic challenge for clinicians, due to lack of understanding of underlying mechanisms. This systematic review explored current literature on therapeutic directions for the following rare genetic bone disorders: fibrous dysplasia, Gorham-Stout syndrome, fibrodysplasia ossificans progressiva, melorheostosis, multiple hereditary exostosis, osteogenesis imperfecta, craniometaphyseal dysplasia, achondroplasia, and hypophosphatasia. The disease mechanisms of Gorham-Stout disease, melorheostosis, and multiple hereditary exostosis are not fully elucidated. Inhibitors of the ACVR1/ALK2 pathway may serve as possible therapeutic intervention for FOP. The use of bisphosphonates and IL-6 inhibitors has been explored to be useful in the treatment of fibrous dysplasia, but more research is warranted. Cell therapy, bisphosphonate polytherapy, and human growth hormone may avert the pathology in osteogenesis imperfecta, but further studies are needed. There are still no current effective treatments for these bone disorders; however, significant promising advances in therapeutic modalities were developed that will limit patient suffering and treat their skeletal disabilities.

Gorham-Stout disease and generalized lymphatic anomalies

We postulate that there exist two distinct lymphatic malformation disorders that affect bones and cause significant morbidity and mortality. Gorham-Stout disease (G-SD) is characterized by the progressive disappearance of trabecular and cortical bone. Generalized lymphatic anomaly (GLA) is characterized by missing areas within trabecular bone and sparing of cortical bone. It is likely that both diseases have a genetic etiology because they often affect multiple noncontiguous sites; however, neither disease is heritable. Both disorders cause focal skeletal fragility. Pleural, pericardial, and peritoneal effusions also frequently complicate these conditions. Case reports and small series suggest that radiation and medical therapies (predominantly interferon and/or bisphosphonates) can stabilize progressive disease. These studies are limited by inconsistent phenotyping, variation in length of therapy and follow-up, and publication bias. We performed a retrospective study of 102 patients who have been referred to our center (24 with G-SD and 78 with GLA). Our data suggest medical therapies may allow remineralization; however, we do not know whether all patients benefit or whether those that do have sustained improvement. Important next steps include a thorough study of natural history and responses to therapy in large patient cohorts, prospective interventional trials with clearly defined outcome measures, and discovery of the genetic cause(s). Recent technologic and analytic advances in DNA and RNA sequencing, improvements in recreating human disease-causing mutations in model organisms, and in high-throughput screening for new therapeutic agents create optimism that the scientific and medical community will soon achieve a detailed understanding of the causes of G-SD and GLA and devise improved therapies for patients.

Gorham-Stout disease and generalized lymphatic anomaly—clinical, radiologic, and histologic differentiation

Gorham-Stout disease (GSD) is a rare vascular disorder of lymphatic origin characterized by progressive osteolysis. Generalized lymphatic anomaly (GLA) is a multisystem disorder that also commonly affects bone. We hypothesized that Gorham-Stout disease is different from other osseous lymphatic anomalies. We proposed to discriminate these entities by analyzing findings on skeletal imaging. Clinical data, imaging studies, and histopathologic findings were retrospectively reviewed in patients presenting to our Vascular Anomalies Center with lymphatic anomalies of bone. Within a cohort of 51 patients with lymphatic disorder and radiological evidence of bony involvement, two distinct categories emerged. Nineteen patients met the imaging criteria for GSD: progressive osteolysis with resorption and cortical loss. Thirty-two were categorized as GLA: Discrete radiolucencies and increasing numbers of bone affected over time, but without evidence of progressive osteolysis. The ribs were the most common site in both groups, followed by the cranium, clavicle, and cervical spine in GSD, and thoracic spine, humerus, and femur in GLA. Fewer bones were involved in GSD, with relative sparing of the appendicular skeleton. Associated infiltrative soft tissue abnormality was seen in 18 in GSD, but only six with GLA. Macrocystic lymphatic malformations were identified in 14 with GLA, but none with GSD. There are significant radiological differences between GSD and GLA, although there are some overlapping features. The major distinguishing characteristic is the progressive osteolysis seen in GSD. Findings suggestive of GLA are more extensive involvement, particularly of the appendicular skeleton, presence of discretemacrocystic lymphatic malformations and visceral organ lesions.

Gorham-Stout disease as a complication of posterior shoulder capsulorrhaphy

Gorham-Stout syndrome (GSS) is a rare condition characterized by rapid onset and massive osteolysis. It can affect any part of the skeleton and is most often seen in children and young adults of either sex; its etiology is unknown. We report a patient in whom GSS developed as a complication of arthroscopically treated posterior shoulder dislocation, review all possible factors to assess whether it was a direct consequence of the procedure or a long-term complication of the dislocation, and discuss the literature.

Successful management of intractable chylothorax in Gorham–Stout disease by awake thoracoscopic surgery

Gorham-Stout is an extremely rare disease, which is characterized by proliferation of vascular and lymphatic bone structures. A 15-year-old male patient was the diagnosis of Gorham-Stout disease of the cervical spine with chylothorax. Awake thoracoscopic ablation was performed using bronchoscopic tools and awake thoracoscopic debridement of the thoracoscopic cavities and chemical pleurodesis with OK-432 were repeated. The amount of drained liquid was controlled. There was no recurrence of pleural effusion.

Gorham-Stout syndrome presenting in a 5-year-old girl with a successful bisphosphonate therapeutic effect

Gorham-Stout syndrome (GSS), also known as Gorham-Stout disease, massive osteolysis, disappearing bone disease or phantom bone, is a rare disorder of the musculo-skeletal system. It most commonly involves the skull, shoulder and pelvic girdle. Histological examination reveals a progressive osteolysis always associated with an angiomatosis of blood vessels and sometimes of lymphatics, which seemingly is responsible for the destruction of the bone. It is extremely rare that Gorham-Stout syndrome involves the bones of the entire body. A 5-year-old girl complaining of intermittent and dull back pain for 3 months was admitted to a local hospital. X-ray revealed left pleural effusion, and the patient was diagnosed with tuberculous pleurisy. Thus, anti-tuberculosis therapy was performed. However, it was not effective. A soft mass with significant tenderness was found in the upper segment of the right leg 50 days afterwards. X-ray revealed multiple osteolysis of the bilateral clavicle, scapula, rib, vertebral body, ilium, sacrum, femur and tibia. The biopsy from the right tibia disclosed that the lesion was composed of hyperplastic blood vessels and fibrous tissues similar to hemangioma. Based on the above clinical, radiological and histopathological findings, the clinical physician confirmed a diagnosis of Gorham-Stout disease, and prescribed oral anti-osteoclastic medications consisting of bisphosphonates. At present, the girl is alive and healthy, and new lesions have not been noted.

Report of a Rare Case of Gorham-Stout Disease of Both Shoulders: Bisphosphonate Treatment and Shoulder Replacement

Massive osteolysis known as Gorham-Stout disease is a rare idiopathic disorder typically affecting long bones in a unifocal pattern. Angiomatosis is strongly connected to the osteolysis. Weather angiomatosis is the cause or the result of osteolysis is subject of intense discussion (Kawasaki et al. (2003), Möller et al. (1999), Radhakrishnan and Rockson (2008)). There are about 200 cases described since 1955. Our patient is a 77-year-old female patient with osteolyses of both shoulders involving the proximal humerus, lateral clavicle, and the glenoid. Under bisphosphonate therapy, the progressive osteolysis stopped on the right side and showed progression on the left. With the patient complaining about severe rest pain and impaired function, we performed surgical reconstruction by implantation of total shoulder prosthesis three months after onset of symptoms. Our case shows a possibility of primary and early surgical reconstruction with good clinical outcome.

Anesthetic management of a pregnant woman with Gorham–Stout disease

Gorham–Stout disease is a rare disorder of bone loss and proliferation of lymphatic and vascular tissue (lymphangiomatosis). A 30-year-old nulliparous woman with Gorham–Stout disease presented at 8 weeks of gestation with a fused cervical spine. At 31 weeks she developed basilar invagination and neurological symptoms that were managed with a neck brace. Anesthetic considerations were those of airway compromise, development of severe preeclampsia and Kasabach–Merritt coagulopathy. Elective tracheostomy was declined. She presented two days before a planned cesarean delivery at 35 weeks in preterm labor. A semi-urgent cesarean delivery under spinal anesthetic proceeded uneventfully, with an otolaryngologist present in case a surgical airway was required. Mother and baby were discharged home after three days. Maternal postpartum recovery was complicated by episodes of respiratory compromise and critical bone loss in the cervical spine, necessitating further surgical reinforcement.

Treatment of Gorham-Stout Disease With Zoledronic Acid and Interferon-α: A Case Report and Literature Review

Gorham-Stout disease is a rare disease characterized by osteolysis, angiomatosis, and soft-tissue swelling. It is a diagnosis of exclusion and has an unknown etiology. Chylothorax is a common complication of the disease that is associated with a high mortality rate. There is no standard of treatment. We report a case of a 16-year-old female with Gorham-Stout disease and recurrent pleural effusions who was successfully treated with concurrent zoledronic acid and peg-interferon α-2b.