Gorham-Stout syndrome, the challenge in diagnosis and unique in treatment: a case report.

BACKGROUND: Gorham-Stout disease is a rare condition with fewer than 400 reported cases in the literature. The presentation of Gorham-Stout disease varies on the basis of location, extent, fracture, and accompanying symptoms. It lacks a specific histopathological appearance but is characterized by vascular changes and the absence of cellular atypia. CASE PRESENTATION: This article presents a case study of a 16-year-old Persian boy with an entire femur with Gorham-Stout disease, highlighting the difficulties in managing this condition. The lack of a clear diagnosis resulted in prolonged procedures, delayed medical treatments, and ultimately required total femoral replacement with an endoprosthesis. CONCLUSION: It is important to note that raising awareness of this disease and its potential complications can facilitate timely and appropriate treatment for patients presenting in the early stages of the disease.

Lymphatic Anomalies in Children: Update on Imaging Diagnosis, Genetics, and Treatment.

Lymphatic anomalies comprise a spectrum of disorders ranging from common localized microcystic and macrocystic lymphatic malformations (LMs) to rare complex lymphatic anomalies, including generalized lymphatic anomaly, Kaposiform lymph-angiomatosis, central conducting lymphatic anomaly, and Gorham-Stout disease. Imaging diagnosis of cystic LMs is generally straightforward, but complex lymphatic anomalies, particularly those with multiorgan involvement or diffuse disease, may be more challenging to diagnose. Complex lymphatic anomalies are rare but associated with high morbidity. Imaging plays an important role in their diagnosis, and radiologists may be the first clinicians to suggest the diagnosis. Furthermore, radiologists are regularly involved in management given the frequent need for image-guided interventions. For these reasons, it is crucial for radiologists to be familiar with the spectrum of entities comprising complex lymphatic anomalies and their typical imaging findings. In this article, we review the imaging findings of lymphatic anomalies, including LMs and complex lymphatic anomalies. We discuss characteristic imaging findings, multimodality imaging techniques used for evaluation, pearls and pitfalls in diagnosis, and potential complications. We also review recently discovered genetic changes underlying lymphatic anomaly development and the advent of new molecularly targeted therapies.

Expanding the spectrum of Gorham Stout disease exploring a single center pediatric case series.

Gorham-Stout Disease (GSD), also named vanishing bone disease, is an ultrarare condition characterized by progressive osteolysis with intraosseous lymphatic vessel proliferation and bone cortical loss. So far, about 300 cases have been reported. It may occur at any age but more commonly affects children and young adults. The aim of this study is to retrospectively review our internal patient series and to hypothesize a diagnostic-therapeutic protocol for earlier diagnosis and treatment. Clinical datasets from our center were examined to identify all GSD patients for collection and analysis. We identified 9 pediatric cases and performed a retrospective case-series review to examine and document both diagnosis and treatment. We found that delay in diagnosis after first symptoms played a critical role in determining morbidity and that multidisciplinary care is key for proper diagnosis and treatment. Our study provides additional insight to improve the critical challenge of early diagnosis and highlights a multidisciplinary treatment approach for the most appropriate management of patients with rare GSD disease. Although GSD is an ultrarare disease, physicians should keep in mind the main clinical features since neglected cases may result in potentially fatal complications.

Abnormal pulmonary lymphatic flow in patients with paediatric pulmonary lymphatic disorders: Diagnosis and treatment.

Pulmonary lymphatic disorders are characterized by the presence of the abnormal lymphatic tissues in the thoracic cavity, presenting clinically as chylothorax, chylopericardium, chyloptysis, interstitial lung disease and plastic bronchitis. These conditions include: neonatal chylothorax, cardiac and non-cardiac plastic bronchitis, non-traumatic chylothorax, post congenital cardiac surgery chylothorax and complex lymphatic malformations. Recently developed lymphatic imaging techniques, such as intranodal lymphangiography and dynamic contrast enhanced magnetic resonance lymphangiography demonstrated abnormal pulmonary lymphatic flow from thoracic duct into pulmonary parenchyma as a pathophysiological mechanism of these diseases. Novel minimally invasive lymphatic interventions, such as thoracic duct embolization, interstitial lymphatic embolization and surgical lympho-venous anastomosis, provide an effective treatment of these conditions.

Complex Lymphatic Anomalies and Therapeutic Options.

Complex lymphatic anomalies include a variety of disorders with overlapping clinical, histological and imaging features. The often-confusing nomenclature used for lymphatic anomalies limits timely diagnosis and treatment. The updated 2018 classification of the International Society for the Study of Vascular Anomalies divides lymphatic anomalies into several subsets.1 Newer imaging techniques including intranodal and magnetic resonance lymphangiography have improved our understanding of anatomy and function of the lymphatic system. Advances in medical, interventional, and surgical treatments have opened a realm of new therapeutic options for patients with complex lymphatic disorders.

Gorham disease of the mandible: a report of two cases and a literature review.

Gorham disease, a rare disorder of unknown etiology, is characterized by the clinical and radiologic disappearance of bone. Because the etiology is unknown, diagnosis is difficult. Therefore, radiographic manifestations play a vital role in the diagnosis of this disease. Thus far, there has been no completely effective treatment. Most remedies are limited to symptom management. Despite the fact that any bone can be affected, one of the most prevalent sites is the maxillofacial region. In this paper, 2 cases of Gorham disease involving the maxillofacial region are reported, including preoperative and postoperative radiographic features.

An overview of the neurosurgical implications, pathophysiology, diagnosis and recent treatment strategies for Grade IV idiopathic osteolysis, also known as Gorham-Stout or phantom bone disease.

OBJECTIVE: Gorham-Stout disease (GSD), commonly referred as vanishing bone or phantom bone disease, is a rare disorder characterized by spontaneous bone osteolysis due to proliferation of lymphangiomatous tissue. This disease can involve multiple bones and cause pathologic fractures. The exact cause of GSD is unknown and its severity is unpredictable; the disorder can potentially cause disfigurement or functional disability. According to CARE guidelines, we studied a 46 years old lady with a progressive defect of the skull. Differential diagnosis included: benign and malignant diploic lesions (eosinophylic granuloma of the skull, myeloma, lytic metastasis from unknown primary tumour, etc) and osteomyelitis. A suspicion of GSD was raised by coupling information from laboratory and nuclear medicine investigations, and eventually confirmed histologically. CONCLUSION: We included early in the investigation protocols a total body fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) scan that was extremely helpful to promptly rule out malignant or infective nature of osteolysis. An update on the diagnostic and management options available for GSD, with particular reference to the role of nuclear medicine and the latest clinical trials from international patients registries and classification of idiopathic osteolysis is provided.

Successful Management of Gorham-Stout Disease in Scapula and Ribs: A Case Report and Literature Review.

Gorham-Stout disease (GSD) is an extremely rare bone condition of unknown etiology characterized by spontaneous and progressive resorption of bones. GSD can occur at any age and is not related to gender, genetic inheritance, or race. Any part of the skeleton can be affected and the symptoms correlate with the sites involved. The diagnosis of GSD is established based on the combination of clinical, radiologic, and histologic features after excluding other diseases. Because of its rarity, current knowledge is limited to case reports and there is no agreement on the best strategy for treatment. The following case report describes a successfully treated case of GSD in a 26-year-old male patient with the left scapula and the 7th-9th left ribs involved. The patient was diagnosed with osteoporosis-related pleural effusion at a local hospital. In our institution, the patient was diagnosed with GSD and treated with radiotherapy and bisphosphonate. The disease was controlled and there was no evidence of disease progression during follow-up. Genetic sequencing was performed to investigate the etiology of GSD. In addition, the present study reviews the theories regarding the etiology, the clinical manifestations, the diagnostic approaches, and treatment options for this rare disease.

Multifocal osteolysis with chylous polyserositis and intrathoracic vein thrombosis: a diagnostic challenge for rheumatologists.

Vanishing bone disease with multisystemic involvement may mimic systemic autoimmune or autoinflammatory diseases. We present a 19-year-old man who was hospitalized due to chest pain following a progressive osteolysis of the bony thorax. The disease later expanded into the pleura, peritoneum and pericardium in a form of massive chylous polyserositis. The patient also developed thrombosis of multiple central veins, which in turn worsened the chylothorax by increasing the pressure in the thoracic duct. This is the first case of vanishing bone disease complicated by triple chylous effusions and central vein thrombosis.

Successful Management of Gorham-Stout Disease in the Cervical Spine by Combined Conservative and Surgical Treatments: A Case Report.

Gorham-Stout disease (GSD) is a rare condition characterized by intraosseous proliferation of endothelial-lined vessels and progressive osteolysis. The precise etiology and pathophysiology of the disease remain poorly understood. Current therapeutic options for GSD include chemotherapy, radiotherapy, and surgical resection, but the surgical treatment of GSD is difficult, especially in the spinal lesion. The indication of wide-margined resection was limited because of anatomical features. Herein, we report a case of GSD of the cervical spine in which the lesions were successfully stabilized with combined conservative and surgical treatments. A 15-year-old male patient was admitted because of severe neck pain. The patient presented no neurological deficiency. However, the radiological findings revealed osteolytic lesions on the laminae and vertebrae between C1 to C5. An open biopsy confirmed an irregular, thin-walled vessel formation in the bone trabeculae, which was diagnosed as GSD. Conservative treatment was initiated with chemotherapy and radiotherapy. After one and a half year, the osteolytic condition had regressed. Spinal fusion surgery was then performed from C2 to C5 to prevent for progression of the cervical kyphotic changes, and spinal fusion was confirmed 7 months after the surgery. The patient showed no recurrence of GSD in the 5-year follow-up period after surgery. We were able to provide successful treatment by giving priority to the combined conservative treatments. If a patient has no severe deformity or progressive neurologic deficits, it might be better to prioritize conservative treatments and to perform the surgery after the osteolytic changes have stopped.

Novel approach of treating Gorham-Stout disease in the humerus--Case report and review of literature.

Gorham-Stout disease or the so-called vanishing bone syndrome is a rare disorder characterized by intra-osseous proliferation of vascular channels resulting in destruction and resorption of the osseous matrix. The exact pathology of this disease showed no evidence of malignant, neuropathic, or infectious components involved in the causation of this disorder except for the culprit of lympho-vascular malformations in the bone. The mechanism of bone resorption is yet to be clarified. The clinical presentation of Gorham's disease varies according to the organ of involvement. Patients diagnosed with Gorham's disease in the bone may initially present with insidious onset of dull aching pain, progressive weakness, or pathologic fractures as the initial presentation. Gorham's disease is progressive in most patients; yet it can be self-limiting in a few reported cases. The axes of treating this disease as reported in the literature include the use of medical treatment, surgical intervention, radiotherapy and/or the combination of any them. However, there is no consensus about the most effective approach for treating this rare disease. The challenge in this disease lies in both: how to diagnose and how to treat. Our novel approach combined surgical intervention, medication and radiotherapy as a treatment of Graham-Stout disease in the humerus, and showed no progression of the disease our case.

Clinical Features and Prognosis of Generalized Lymphatic Anomaly, Kaposiform Lymphangiomatosis, and Gorham-Stout Disease.

BACKGROUND: Complex lymphatic anomalies are intractable lymphatic disorders, including generalized lymphatic anomaly (GLA), Gorham-Stout disease (GSD), and kaposiform lymphangiomatosis (KLA). The etiology of these diseases remains unknown and diagnosis is confused by their similar clinical findings. This study aimed to clarify the differences in clinical features and prognosis among GLA, KLA, and GSD, in Japanese patients. PROCEDURE: Clinical features, radiological and pathological findings, treatment, and prognosis of patients were obtained from a questionnaire sent to 39 Japanese hospitals. We divided the patients into three groups according to radiological findings of bone lesions and pathology. Differences in clinical findings and prognosis were analyzed. RESULTS: Eighty-five patients were registered: 35 GLA, 9 KLA, and 41 GSD. Disease onset was more common in the first two decades of life (69 cases). In GSD, osteolytic lesions were progressive and consecutive. In GLA and KLA, 18 patients had osteolytic lesions that were multifocal and nonprogressive osteolysis. Thoracic symptoms, splenic involvement, and ascites were more frequent in GLA and KLA than in GSD. Hemorrhagic pericardial and pleural effusions were more frequent in KLA than GLA. GSD had a significantly favorable outcome compared with combined GLA and KLA (P = 0.0005). KLA had a significantly poorer outcome than GLA (P = 0.0268). CONCLUSIONS: This survey revealed the clinical features and prognosis of patients with GLA, KLA, and GSD. Early diagnosis and treatment of KLA are crucial because KLA has high mortality. Further prospective studies to risk-stratify complex lymphatic anomalies and optimize management for KLA are urgently needed.

Gorham's disease of the proximal tibia successfully treated with local administration of OK-432, followed by reconstruction with distraction osteogenesis: a case report.

Gorham's disease (GD) is a rare and intractable disease characterized by marked progression of osteolysis associated with lymphangioma and/or hemangioma. Here, we describe a case of GD of the proximal tibia occurring in a 10-year-old boy. Although we could not correctly diagnose it at first, we finally diagnosed him as having GD. Progression of osteolysis of the tibia stopped 3 months after the local administration of OK-432. Thereafter, the huge bone defect with varus and extension deformity was reconstructed successfully by distraction osteogenesis using the Ilizarov method. The present case suggests that local administration of OK-432, followed by distraction osteogenesis is a treatment option for GD.

[Lymphangiomatosis and Gorham-Stout disease].

Lymphangiomatosis (recently renamed "generalized lymphatic anomaly") is a rare disease of unknown etiology that features an increase in the number of lymphatic vessels in many different tissues. Gorham-Stout disease(GSD) is a related disease characterized by lymphatic vessels involving the bones and resulting in progressive bone destruction. Respective definitions remain unclear because these conditions largely overlap in the clinical setting and are both associated with pleural effusion and other visceral lesions. These two conditions have recently been differentiated based on imaging findings. GSD is characterized by progressive osteolysis with loss of cortical bone. These diseases present considerable diagnostic and therapeutic challenges. Implementation of basic and clinical research is mandatory to improve understanding of these conditions and optimize management.

Fatal Progression of Gorham Disease: A Case Report and Review of the Literature.

Gorham disease is an idiopathic massive osteolysis, and maxillofacial involvement is rare. This report describes a case of a 12-year-old boy with severe progressive osteolysis in the mandible, hyoid bone, mastoid process, and cervical spine. Radiation therapy and interferon-α therapy were followed by bisphosphonate therapy. The patient died of respiratory failure. To describe the clinicopathologic features of Gorham disease of the jaws with an emphasis on the fatal types, 64 cases in the literature were reviewed (female-to-male ratio, 1:1.78; average age, 33.02 ± 19.38 yr). Most lesions were located only in the mandible or in other locations in combination with the mandible, except for 3 cases. During follow-up, there were 7 cases of disease-specific death, resulting in a mortality rate of 10.94%. The main causes of death were chylothorax, rib fractures secondary to osteolysis, or spinal fractures. Although most patients received surgical treatment (43.75%), the type of treatment was not related to prognosis.

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's disease in the metatarsus: a case report.

Gorham-Stout disease (GSD) is a rare disease occurring in the bone tissue and is characterized by spontaneous, progressive resorption. The etiology and treatment of the disease remains unclear. This article presents a 53-year-old male patient diagnosed with GSD in the 3rd and 4th metatarsal of his right foot.