Epidural Hematoma related to lower limb pain and massive liver bleeding in Gorham-Stout disease: A case report.

RATIONALE: Gorham-Stout disease (GSD) is a rare disease that causes massive osteolysis and proliferation of abnormal lymphangiomatous tissues. Patients with GSD often experience pain associated with bone fractures and chylothorax. However, bleeding caused by abnormal lymphangiomatous tissue or hematological dysfunction rarely occurs. PATIENT CONCERNS: A 22-year-old female patient with GSD presented with severe left hip and lower limb pain. The GSD had disappeared her right pelvic bone and femur, but no abnormalities were found in the bones at the site of the pain. DIAGNOSES: The patient presented with a chylothorax and cerebrospinal fluid leakage. She was treated with sirolimus and an epidural blood patch, and her symptoms resolved. Computed tomography and magnetic resonance imaging revealed an epidural hematoma extending from L3 to the caudal region, and blood results revealed a consumption coagulopathy. INTERVENTIONS: We presumed that the hematoma caused pain and prescribed pregabalin and morphine. The pain gradually subsided. OUTCOMES: An unexpected liver subcapsular hemorrhage occurred 4 months later, and the patient went into hemorrhagic shock. Transcatheter arterial embolization was promptly performed, and the patient recovered. LESSONS: GSD infrequently causes bleeding related to abnormal lymphangiomatous tissues and coagulopathy, yet it can lead to serious events if it occurs.

The molecular mechanism of Gorham syndrome: an update.

Gorham syndrome, also known as "vanishing osteopathy" and "invasive hemangiomatosis," is a rare clinical syndrome whose etiology is unknown and can invade the whole-body skeleton. At present, more than 300 cases have been reported at home and abroad, usually manifesting as spontaneous chronic osteolysis with no periosteal reaction at the lysis site and occult onset, often with fractures, scoliosis, chylothorax, etc. When waiting for medical treatment, the condition is serious, and the prognosis is poor. At present, there is no effective treatment. The main pathological manifestations of Gorham syndrome are the non-neoplastic abnormal proliferation of lymphatic vessels or blood vessels and osteolysis caused by osteoclast proliferation or increased activity. At present, there is no unified conclusion regarding Gorham syndrome's pathogenesis. This paper starts with the two most studied osteolysis methods at present, osteoclast osteolysis and osteolysis caused by vascular and lymphatic proliferation and summarizes the corresponding most possible molecular mechanisms in recent years to provide more ideas for Gorham syndrome treatment.

Gorham-Stout disease affecting the spine with cerebrospinal fluid leakage and Chiari-like tonsillar herniation: a rare case report and review of literature.

BACKGROUND: Gorham-Stout disease (GSD) is a very rare disorder characterized by massive osteolysis of poorly understood aetiology. The association between GSD involving the skull base and cerebrospinal fluid (CSF) leakage has been reported in the literature. However, few cases of CSF leakage and Chiari-like tonsillar herniation in GSD involving the spine have been reported. CASE PRESENTATION: We present the case of a 20-year-old man with GSD involving the thoracic and lumbar spine, which caused CSF leakage and Chiari-like tonsillar herniation. The patient underwent four spinal surgeries for osteolytic lesions of the spine over a 10-year period. Here, we discuss the possible aetiology of the development of CSF leakage. Epidural blood patch (EBP) was performed at the T11-T12 level to repair the CSF leakage. After EBP treatment, rebound intracranial hypertension (RIH) developed, and tonsillar herniation disappeared 2 months later. CONCLUSIONS: GSD involving the spine with CSF leakage and Chiari-like tonsillar herniation is relatively rare. For patients who have undergone multiple spinal surgeries, minimally invasive treatment is an alternative treatment for CSF leakage. EBP can repair CSF leakage secondary to GSD and improve chronic brain sagging, with reversibility of Chiari-like malformations.

Gorham-Stout syndrome: A chylothorax disease with bony destruction: A case report.

RATIONALE: Gorham-Stout syndrome is a sporadic condition characterized by a tumor-like lesion with extensive osteolysis, severe symptoms, and a poor prognosis. Poor prognostic indicators include osteolytic lesions of the spine and pleura effusion. PATIENT CONCERNS: A 67-year-old Chinese man with five months history of chest tightness presented to our institution with aggravated shortness of breath. Ultrasonography demonstrated hydrothorax on the right side. The patient's imaging studies (computerized tomography [CT] scan, magnetic resonance imaging, and positron emission tomography [PET]/CT) revealed osteolytic lesions (the skull, several spines, several ribs, both shoulder blades, and the pelvis). DIAGNOSES: Gorham-Stout syndrome. (4) Interventions: We advised the patient to follow a low-fat diet. On the patient, we performed a superior vena cava angiography. The injection of zoledronic acid was used to prevent bone loss. OUTCOMES: We found resolution of chylothorax after a low-fat diet, superior vena cava angiography and injection of zoledronic acid. LESSONS: The possibility of Gorham -Stout syndrome should be ruled out in patients with clinical chylothorax. The relief of chylothorax requires comprehensive treatment.

[Complicated lymphatic anomaly: a clinicopathological analysis of four cases].

Objective: To investigate the clinicopathological features, clinical manifestations and different diagnosis of patients with complicated lymphatic anomaly. Methods: The clinical and pathologic data of four patients with complicated lymphatic anomaly diagnosed and treated in Peking Union Medical College Hospital from January 2000 to December 2021 were collected and analyzed. Results: One Gorham-Stout disease case and three generalized lymphatic anomaly cases were included in this cohort. Patients' ages ranged from 7 to 32 years. There were three males and one female. The positions of biopsy included three bone biopsy and one bronchus biopsy. Microscopically, all cases showed diffuse enlarged lymphatic channels. At the same time, osteogenesis was obvious in Gorham-Stout disease case. Radiologically, cortical loss was seen in Gorham-Stout disease, and lytic bone confined to the medullary cavity presented in generalized lymphatic anomaly. The three generalized lymphatic anomaly cases also had coagulopathy, and two had effusion. Conclusions: The histologic feature of complicated lymphatic anomaly was diffuse lymphatic malformation, and the diagnosis depends on clinical and pathologic information. The treatment and prognosis of these diseases are different, and therefore it is necessary to understand their clinical and pathologic features and make the correct diagnosis.

Gorham-Stout case report: a multi-omic analysis reveals recurrent fusions as new potential drivers of the disease.

BACKGROUND: Gorham-Stout disease is a rare condition characterized by vascular proliferation and the massive destruction of bone tissue. With less than 400 cases in the literature of Gorham-Stout syndrome, we performed a unique study combining whole-genome sequencing and RNA-Seq to probe the genomic features and differentially expressed pathways of a presented case, revealing new possible drivers and biomarkers of the disease. CASE PRESENTATION: We present a case report of a white 45-year-old female patient with marked bone loss of the left humerus associated with vascular proliferation, diagnosed with Gorham-Stout disease. The analysis of whole-genome sequencing showed a dominance of large structural DNA rearrangements. Particularly, rearrangements in chromosomes seven, twelve, and twenty could contribute to the development of the disease, especially a gene fusion involving ATG101 that could affect macroautophagy. The study of RNA-sequencing data from the patient uncovered the PI3K/AKT/mTOR pathway as the most affected signaling cascade in the Gorham-Stout lesional tissue. Furthermore, M2 macrophage infiltration was detected using immunohistochemical staining and confirmed by deconvolution of the RNA-seq expression data. CONCLUSIONS: The way that DNA and RNA aberrations lead to Gorham-Stout disease is poorly understood due to the limited number of studies focusing on this rare disease. Our study provides the first glimpse into this facet of the disease, exposing new possible therapeutic targets and facilitating the clinicopathological diagnosis of Gorham-Stout disease.

Gorham-Stout disease of skull base leading to cranial settling and rhinorrhea: a case-based review.

PURPOSE: Gorham-Stout disease (GSD) is a rare progressive osteolytic disorder, theoretically caused by lymphovascular endothelial proliferation. Spinal involvement carries a dismal prognosis because of neurological consequences. Lesions of the skull base are extremely rare and entail even more devastating prognosis due to cervical instability and cerebrospinal fluid (CSF) leakage. Due to scarcity of this condition, the aim of this study was to give an overview of skull base GSD and review the cases with such condition reported in the literature. METHODS: In this case-based review, different aspects of skull base GSD are discussed, and a sample clinical case of GSD leading to cranial settling and rhinorrhea is presented. The characteristics, symptoms, and managements of all English-language PubMed-reported cases were reviewed, and different features of presentation and methods of treatments were analyzed. RESULTS: Based on the literature review, most of the cases encountered serious problems in the course of the disease. Meningitis/CSF leakage was detected in 12 of 26 collected cases, followed by hearing loss/tinnitus/otitis media in 10 cases, headache in 8, and neck pain/stiffness in 8 patients. Despite a variety of treatments, improvement was only observed in 8 of 26 collected cases. The reminders showed either stable condition or worsening and death. CONCLUSION: All cases of GSD of the skull base should be evaluated for rhinorrhea/otorrhea and cranial settling, both of them being among the most life-threatening conditions. Since definite treatment, in order to stop disease progression, is sometimes impossible, symptomatic and supportive treatment should be started as possible.

Gorham Stout disease of the temporal bone with cerebrospinal fluid leak.

Gorham Stout disease (GSD) is a rare disease characterized by the proliferation of endothelial lined vessels and replacement of bone by fibrous tissue. The main imaging features are progressive osteolysis and cortical resorption. Temporal bone involvement is rare but presents as a destructive bone lesion that may be misinterpreted as more common lytic processes in the pediatric population, such as infection or Langerhans cell histiocytosis. GSD of the temporal bone is associated with cerebrospinal fluid (CSF) leaks, may present with otorrhea, and can mimic other causes of ear drainage. Here, we report the clinical course, imaging features, and outcomes of a 3-year-old girl with GSD of the temporal bone presenting with CSF leak initially attributed to infection.

Gorham-Stout disease of the mandible, manubrium and cervical spine presenting as bilateral chylothorax.

Gorham-Stout disease (GSD) is an extremely rare musculoskeletal disease of unknown aetiology characterised by non-neoplastic proliferation of vascular and lymphatic channels causing massive osteolysis, typically affecting younger individuals. Chylothorax is a known complication of GSD which is postulated to occur from thoracic spine involvement leading to pleural or thoracic duct invasion. In our case, bilateral chylothorax developed in a 60-year-old woman without any thoracic spine involvement of her disease, challenging the proposed mechanism. Despite bilateral pleural drainage and escalating doses of sirolimus, she ultimately developed respiratory failure and shock and succumbed to her illness. Overall survival of GSD is unknown, but when complicated by chylothorax, prognosis is typically poor. GSD represents a diagnostic and management challenge due to the paucity of knowledge surrounding its aetiology and management. These patients require multidisciplinary coordinated care. It is also important to note its high mortality when associated with chylothorax in particular.

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.

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

BACKGROUND: Gorham-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 PRESENTATION: A 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. CONCLUSION: This 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.

A Large Skull Defect Due to Gorham-Stout Disease: Case Report and Literature Review on Pathogenesis, Diagnosis, and Treatment.

A 24-year old man was referred to the Erasmus MC Bone Center because of an asymptomatic increasing skull defect of the left parietal bone. The defect was first noticed at the age of six, and gradually increased over the years. His medical history was unremarkable, without any known trauma and a negative family history for bone diseases. Laboratory tests showed a low vitamin D level without other abnormalities. Particularly, there was no increase in markers of inflammation or bone turnover. CT-scans of the skull showed an osteolytic region of the parietal skull bone, with a two-centimeter increase in diameter over 9 years. Contrast enhanced MRI showed lymphangiogenic invasion, which was compatible with our suspicion of Gorham-Stout disease. The patient was referred to the neurosurgeon for treatment with a bone graft while considering additional drug treatment. Gorham-Stout or vanishing bone disease is a rare entity characterized by progressive osteolysis with lymphangiogenic bone invasion. Although already reported in 1838, currently the diagnosis and treatment of Gorham-Stout disease is still challenging. The underlying pathophysiology is not clarified yet and several theories exist. The disease usually affects persons younger than 40 years and the majority present with bone disease of the maxillofacial region, the upper extremities or the torso. The clinical presentation includes most frequently pain, swelling, and functional impairment of the affected region, but the disease can also be asymptomatic. Laboratory investigations are usually normal, and diagnosis is based upon imaging and sometimes pathology examination of affected bone tissue. Treatment is experimental and there is no general consensus about the best option due to lack of randomized controlled trials. Case reports showed patients treated with bisphosphonates, interferon-alpha, anti-VEGF therapy, mTOR inhibitors, and radiotherapy. There are some reports of surgery with prosthetic or bone grafts but no long-term follow-up data exist. This paper describes a unique case of Gorham-Stout disease of the parietal skull bone and discusses the current state of knowledge about this rare bone disease.

Unusual case of chylothorax with unilateral limb swelling.

Here, we present an unusual case of 26-month male toddler who presented with swelling of right lower limb with painless hyperpigmented patch over right groin of 18 months duration associated with recent onset respiratory distress. Evaluation revealed right chylothorax and MRI revealed altered signal intensity in bones and muscles of right lower limb. Lymphoscintigraphy revealed absence of lymphatic channels in right lower limb. Skin biopsy from hyperpigmented patch was suggestive of vasoformative lesion favouring lymphangiomatosis. A diagnosis of Gorham's syndrome was made, and our patient was managed with drainage of chylothorax followed by pleurodesis, parenteral nutrition and radiotherapy.

Multifocal Gorham-Stout disease associated with Chiari I malformation and recurrent aseptic meningitis: Case report and review of literature.

Gorham-Stout disease is a rare condition of uncertain aetiology characterised by lymphatic proliferation within osseous structures and subsequent massive osteolysis. This report describes the index case of a patient with multifocal Gorham-Stout disease involving the skull base with Chiari I malformation and recurrent aseptic meningitis without fistula. A five-year-old male presented following decompression of a Chiari I malformation with headaches, vomiting, and stiff neck and cerebrospinal fluid pleocytosis without growth of a pathogenic organism. Ongoing symptoms prompted a further three presentations over several months revealing persistent aseptic cerebrospinal fluid monocytic pleocytosis. Further investigation revealed multifocal osseous cystic disease and subsequent bone biopsy suggested Gorham-Stout disease. Suboccipital decompression was not repeated despite craniocervical junction re-stenosis. A literature review demonstrated the extreme rarity of Gorham-Stout disease associated with Chiari I malformation and meningitis. Potential mechanisms of these entities occurring in concert are discussed. Consideration of Gorham-Stout disease as a secondary cause for Chiari I malformation is important amid local bone changes or cerebrospinal fluid leakage prior to pursuing suboccipital decompression considering the poor outcomes reported.

A report of two children with Gorham-Stout disease.

BACKGROUND: Gorham-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 REPORTS: We 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. CONCLUSION: Diagnosis of Gorham-Stout disease is made by exclusion, and its clinical presentation varies widely, from spontaneous remission to a fatal outcome.

Surgical Management of Gorham-Stout Disease in Cervical Compression Fracture with Cervicothoracic Fusion: Case Report and Review of Literature.

BACKGROUND: Gorham-Stout disease (GSD) or "vanishing bone" disease is characterized by progressive osteolysis with intraosseous lymphangiomatosis (hemangiomatosis). Given its rarity, with about 300 reported cases, its pathophysiology, etiology, and treatment guidelines are not established yet. CASE DESCRIPTION: A 22-year-old man was admitted to Severance Hospital with the chief complaint of neck pain from an injury due to falling. Initial cervical radiography showed a C4 burst fracture, and cervical magnetic resonance imaging revealed diffuse osteolytic lesions with coarse trabeculation with T2 hyperintensity and T1 enhancement in the entire cervical and upper thoracic area. He had a previous history of chylothorax that was still noticeable on a chest radiograph at the time of admission. A 2-stage operation was conducted. First, anterior corpectomy of C4 and anterior plate fixation of C3-5 were performed. Second, a week later, posterior fixation of C3-5 was performed. Thereafter, the patient was discharged without any neurologic complications. However, during the 1-month follow-up, asymptomatic progressive kyphosis was detected via radiography, and posterior cervical fusion of C2-T4 was performed. A minimal postoperative symptom of an intermittent left arm pain of 4-5 on the visual analog scale was experienced. No further deformity progression was noted until the last outpatient follow-up. CONCLUSIONS: Spinal GSD can cause severe deformity and neurologic deficits such as paralysis. Although treatment for GSD is not established, surgical treatment is recommended in severe deformity or aggravated neurologic deficit. The appropriate timing of surgery is after the arrest of osteolysis. Magnetic resonance imaging could be helpful in determining stable GSD.

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

BACKGROUND: Gorham-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. METHODS: Retrospective 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. RESULTS: 6 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. CONCLUSION: Main 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.

99mTc-SC lymphoscintigraphy and SPECT/CT findings in a case report of Gorham-Stout disease presenting with chylothorax and bone pain.

RATIONALE: Gorham-Stout disease (GSD) is a rare disorder characterized by multiple osteolytic lesions, sometimes complicated by chylothorax. The aim of this case report is to introduce a very rare case of Gorham-Stout syndrome, which involved several bones along with chylous pericardial and pleural effusions detected by Tc-sulfur colloid (SC) lymphoscintigraphy and single photon emission computed tomography/computed tomography (SPECT/CT). PATIENT CONCERNS: A 15-year-old girl presented to our hospital complaining of shortness of breath and bone pain. DIAGNOSIS: The CT showed multiple osteolytic lesions, left-sided pleural effusion, and pericardial effusion. Tc-SC lymphoscintigraphy showed discontinuation of thoracic duct and tracer accumulation on the left side chest. SPECT/CT revealed increased radioactivity uptake in pleural, pericardial effusions, and some thoracolumbar spines. Diagnostic thoracentesis to identify the nature of pleural effusion and histopathology of biopsy in the right femoral to that of the bone lesion were performed. Based on the clinical information, histopathologic, and radiographic findings, the diagnosis of GSD was made. INTERVENTIONS: The patient received thoracic duct ligation and bisphosphonates treatment. OUTCOMES: After receiving thoracic duct ligation and bisphosphonates treatment, the patient's symptoms of bone pain and dyspnea were relieved, and the pericardial and pleural fluid was diminished dramatically. At the 3-month and 9-month follow-up visit, the patient had nearly complete remission without any complication. LESSONS: The Tc-SC lymphoscintigraphy and SPECT/CT could provide significant value assessing the lymphatic abnormity and evaluating the extent of disease, therefore aiding to guide decision making in the clinic.