|Year : 2019 | Volume
| Issue : 3 | Page : 62-65
Management of Gorham–Stout disease presenting as intractable pleural effusion in an adolescent: A case report and review of literature
TK Jayakumar1, Daisy Khera2, Vivek Manchanda1, Kirtikumar J Rathod1
1 Department of Pediatric Surgery, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
2 Department of Pediatric Medicine, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
|Date of Web Publication||27-Dec-2019|
Dr. Kirtikumar J Rathod
Department of Pediatric Surgery, All India Institute of Medical Sciences, Jodhpur, Rajasthan
Source of Support: None, Conflict of Interest: None
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.
Keywords: Chylothorax, Gorham–Stout disease, osteolysis, sirolimus
|How to cite this article:|
Jayakumar T K, Khera D, Manchanda V, Rathod KJ. Management of Gorham–Stout disease presenting as intractable pleural effusion in an adolescent: A case report and review of literature. Oncol J India 2019;3:62-5
|How to cite this URL:|
Jayakumar T K, Khera D, Manchanda V, Rathod KJ. Management of Gorham–Stout disease presenting as intractable pleural effusion in an adolescent: A case report and review of literature. Oncol J India [serial online] 2019 [cited 2020 Jan 21];3:62-5. Available from: http://www.ojionline.org/text.asp?2019/3/3/62/274092
| Introduction|| |
Gorham–Stout disease (GSD) is a rare disorder, in which there is an abnormal proliferation of endothelial-lined vessels in multiple organs with osteolysis being the most characteristic feature. Nearly 185 cases have been reported till date. Owing to its rarity, underreporting, and lack of extensive research, treatment options are limited. In this report, we describe one such unique case which presented with extensive swelling in trunk, left upper limb, and absent sternum later diagnosed to be GSD and managed successfully with sirolimus.
| Case Report|| |
A 15-year-old male presented with a complaint of progressively increasing shortness of breath for 3 years. On examination, he was severely malnourished and had excessive thoracic kyphosis, and a large swelling that involves abdomen wall (anteriorly and posteriorly), left side of the chest wall, and left upper limb. Skin over the anterior chest had 15-cm violaceous patch. Sternum was absent, and cardiac pulsations were visible. Appearance of the chest and abdomen at the time of presentation was shown in [Figure 1]. In the past, a swelling over the chest was excised in other institutes, 2 years ago. A chest X-ray revealed a bilateral pleural effusion, and there is absence of sternum and anterior ribs [Figure 2]a. X-ray of the left upper limb revealed a complete destruction of the left humerus was completely destroyed, and radius and ulna had cortical and medullary osteolytic lesions [Figure 2]b. The left intercostal drain was inserted, which drains lymphatic (creamy-pink color) fluid. It were protein and triglyceride rich, with lymphocyte predominance. As intercostal drainage was done, swelling in the abdomen also subsided. Later, he required right-sided chest drain and subcutaneous drain in abdomen to relieve dyspnea. Computed tomography scan showed bilateral massive pleural effusion, compression fracture of vertebrae owing to vascular lesions within. Initially, assumed to be a lymphatic malformation, based on the clinical features, treatment results for the same were not satisfactory. Literature search for chylothorax and osteolysis introduced us to GSD.
|Figure 1: Appearance of the chest and abdomen at the time of presentation|
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|Figure 2: (a) Chest X-ray showing bilateral pleural effusion, absent sternum and anterior ribs. (b) X-ray of the left humerus shows osteolytic lesions and severe osteopenia|
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Sirolimus therapy with dose of 1 mg twice daily was started in addition to bleomycin intralesional injections. The patient had a turbulent clinical course due to respiratory failure once, requiring tracheostomy, mechanical ventilation, and intensive care unit care. Over 2 months, the patient was gradually weaned off the ventilator and kept on BiPAP ventilation. Eventually, the condition of the patient has improved, and tracheostomy was decannulated gradually. Addition of sirolimus to the treatment had shown a significant change in the clinical condition of the patient. The swelling had subsided; there was no palpable mass in the chest or abdomen. Chylothorax has subsided for the patient [Figure 3]a. A thoracic brace was made to protect the chest and the spine from inadvertent trauma, and the patient was discharged on sirolimus therapy [Figure 3]b. He is on follow-up for the past 10 months and has been asymptomatic.
|Figure 3: Patient's appearance at the time of discharge showing resolved swelling of the trunk (a) and the presence of chest brace for protection (b)|
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| Discussion|| |
First described by JBS Jackson in 1838, Gorham and Stout published the first detailed report on GSD in 1955. GSD can present at any age, that is, 7 months–83 years, but mostly in children and young adults, with unclear sex predilection (male to female = 1.6:1) and undefined inheritance pattern. Symptoms of presentation include swelling, pain, weakness, and functional disability of involved regions, shortness of breath (most distressful), neurological deficits, and deformity. Commonly affected bones include maxilla, mandible, ribs, sternum, clavicle, vertebrae, pelvis and femur, and other extremities., Solitary osteolytic lesions coalesce overtime, giving sucked candy appearance in tubular bones, complete resorption, and replacement by fibrous tissue. Nearly 25% of GSD patients have chylothorax, causing mild distress to respiratory failure as in our case. Chylothorax is associated with increased risk of mortality. Involvement of vertebrae can cause deformity and neurological deficits. Heffez et al. suggested diagnostic criteria to differentiate GSD from generalized lymphatic anomaly such as: (1) positive biopsy with presence of angiomatous tissue, (2) absence of cellular atypia, (3) minimal or no osteoblastic response or dystrophic calcification, (4) evidence of progressive osseous resorption of involved bone, (5) nonexpansile, nonulcerative lesions, (6) no involvement of viscera, (7) osteolytic radiographic pattern, and (8) negative hereditary, metabolic, neoplastic, immunologic, or infectious etiology.
Etiology is not completely understood. Gorham and Stout reported that there was diffuse proliferation of endothelial-lined vessels in affected bones and fibrous tissue. Immunohistochemical markers LYVE-1 and podoplanin which are present on lymphatic endothelial cells were found in the bones and tissues affected by GSD, confirming that the proliferating vessels to be lymphatic. Absence of MIB-1 (antibody against proliferation marker Ki-67) labeling meant that GSD is a malformation rather than tumor as mentioned in the International Society for the Study of Vascular Anomalies classification system. Lymphatic proliferation from pre-existing lymphatic channels (lymphangiogenesis) occurs in an uncontrolled fashion. It is attributed to increase the levels of pro-lymphangiogenic factors, vascular endothelial growth factor (VEGF)-C and VEGF-A and decrease the levels of anti-lymphangiogenic factors (Svegfr2, transforming growth factor-beta, and interferon [IFN] gamma). These elevated factors were found to be secreted by macrophage-like cells which serve as osteoclasts, rather than osteoclasts themselves. Another striking feature is absence of osteoblasts activity in diseased regions. In diseases with bone resorption, there is an increased activity of osteoblasts, which replace the lost bone with a new bone. Rather than stimulating osteoblast repair response, mesenchymal progenitors are stimulated in GSD, leading to deposition of fibrous tissue.
GSD cases with chest involvement are shown in [Table 1]. Treatment options for GSD are limited, which include surgeries, radiotherapy, and pharmacotherapy. Surgeries are aimed at halting the disease progression and symptom relief, with pleurectomy, pleurodesis, thoracentesis, and thoracic duct embolization/ligation. The use of radiotherapy has been described with success rate in localized lesions being about 75%. Pharmacotherapy includes bisphosphonates, IFN alpha-2b, in combination with anti-VEGF-A antibodies, bevacizumab, propranolol, low-molecular-weight heparin, steroids, Vitamin-D, and calcitonin. Mammalian target of rapamycin inhibitor is still in Phase 2 clinical trials, preliminary results were promising.
GSD is easy to miss, as it clinically appears to be like a lymphatic anomaly. Our patient was symptomatic for 3 years, received various treatments. The diagnosis was made during his admission in our facility. Untreated patients experience a severe morbidity and mortality in those with chylothorax. Lymphatic anomaly with osteolytic lesions should point toward the diagnosis of GSD. Earlier diagnosis may improve the prognosis in these patients.
| Conclusion|| |
GSD is a rare disease, and knowledge is essential for its suspicion and diagnosis. Sirolimus may be an effective therapy for complex vascular malformations, including GSD. Supportive management including multispecialty care is necessary for good outcome in such patients.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]