Gorham-Stout syndrome: a chylothorax disease with massive bony destruction

doi:10.21203/rs.3.rs-1501512/v1

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Gorham-Stout syndrome: a chylothorax disease with massive bony destruction

https://doi.org/10.21203/rs.3.rs-1501512/v1

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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. We presented a case in which the condition first manifested itself at the age of 67, with exacerbated shortness of breath. The patient's imaging studies (CT scan, MRI, and PET/CT) revealed osteolytic lesions (the skull, several spines, several ribs, both shoulder blades, and the pelvis). After a tissue biopsy of the spine, postoperative pathology revealed that a portion of the bone had been replaced by lymphatic-derived endothelial cells that stained positive for D2-40. The tests permitted parasitosis, thyroid or parathyroid disease, parasitosis, lymphoma, neoplasia, or an autoimmune problem to be ruled out. On the patient, we performed a superior vena cava angiography. There was an abnormal expansion of the azygos vein into the superior vena cava, as well as local contrast agent retention. The injection of zoledronic acid was used to prevent bone loss. After the therapy, his shortness of breath was greatly reduced. He experienced ongoing shortness of breath alleviation during the 2-month follow-up visit.

Gorham–Stout syndrome

chylothorax

osteolysis

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 of the right side. Thoracentesis was performed, and the test results confirmed chylothorax (Fig. 1) (lactate dehydrogenase, 143.8 U/L; glucose, 5.92mmol/L; protein, 48.7g/L; adenosine deaminase, 8.3U/L, positive chylous test, negative cultures; cell count with 98% mononuclear cells and negative biopsy for cancer). A computed tomographic scan, whole-body scan, and positron emission tomography-computed tomography demonstrated massive bony destruction of the skull, several spines, several ribs, both shoulder blades, and the pelvis (Fig. 2).

The tumor markers carbohydrate antigen (CA) 125, CA 19 − 9 value, CA15-3, CA 72 − 4, carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), neuron-specific enolase (NSE), alpha-fetoprotein (AFP), and prostate-specific antigen (PSA) had values within the normal range. Average values of serological markers of autoimmunity, creatine kinase-MB (CKMB), rheumatoid factor, antithyroglobulin antibody, and circulating immune complexes (CIC) excluded autoimmunity. The markers of myocardial injury, liver, and kidney function were normal. The indicators associated with tuberculosis were normal. The laboratory tests showed no increase in inflammation markers. No signs of tumor were found by thoracoscopy (Fig. 3), gastroscopy, and colonoscopy. No particular relevant circumstances regarding his family history were identified. A tissue biopsy of the spine was performed, and the postoperative pathology confirmed that part of the bone was replaced by lymphatic-derived endothelial cells, which were positive for D2-40 staining (Fig. 4).

The diagnosis of Gorham-Stout disease¹ was established based on the clinical and imaging elements and the exclusion of pathologies such as parasitosis, thyroid or parathyroid disease, parasitosis, lymphoma, neoplasia, and autoimmune disorder. We performed a superior vena cava angiography on the patient. Abnormal enlargement of azygos vein into superior vena cava and local contrast agent retention was observed. The zoledronic acid injection was used to inhibit bone destruction. His shortness of breath relieved significantly after the therapy. At the 2-months follow-up visit, he reported continuous shortness of breath relief.

Gorham–Stout syndrome, characterized by a tumor-like lesion with large osteolysis, is sporadic with severe symptoms and poor prognosis ^1,2. Local swelling can occur when the lesion invades the soft tissue surrounding the bone, and chylothorax can occur when the lesion invades the chest wall, ribs, vertebrae, or thoracic duct³. Gorham–Stout syndrome's etiology and pathogenesis remain uncertain and controversial⁴. The existence and role of osteoclasts and vascular and lymphatic vessels have been controversial in the pathogenesis of Gorham–Stout syndrome ^5–8.

Clinical manifestations of Gorham–Stout syndrome vary, with onset ages reported ranging from 1 month to 92 years. The severity of the disease usually depends on the involved structures and the progression of osteolysis, and there are generally no systemic symptoms ^9,10. Past trauma has been mentioned in specific individuals ¹¹. There was no history of trauma in our case, and the disease began after the age of 65.

Localized discomfort, swelling, weakness, functional impairment of afflicted limbs, respiratory distress and failure, neurological problems, deformities, and paralysis are among symptoms that can be seen in Gorham–Stout syndrome. Areas commonly affected by Gorham–Stout syndrome include the ribs, spine, pelvis, limb bones, shoulder blades¹². This case was characterized by progressive dyspnea, and the symptoms caused by bone destruction were not obvious.

In addition to conventional X-ray, CT, and MRI, bone scan, SPECT/CT, and PET/CT can also be used for imaging examination of Gorham–Stout syndrome³. X-rays usually show bone absorption but no periosteal reaction. CT scan can show the location and number of osteolytic lesions more clearly than X-ray¹³. 18F-NaF-PET/CT showed higher consistency in Gorham–Stout syndrome lesions, opening new possibilities for diagnosis, degree of disease activity, and treatment response ¹⁴. Our case contains multiple bone lesions consistent with the typical presentation of Gorham–Stout syndrome.

Pathological diagnosis is essential for the diagnosis of Gorham–Stout syndrome. The pathological findings are closely related to the site of the specimen. The typical pathological findings are bone resorption and replacement by vascular or lymphatic thin-walled monolayer endothelial cells, accompanied by infiltration of lymphatic and vascular soft tissue, without cellular atypia and inflammatory infiltration³. Immunohistochemistry shows that D2-40 intense staining of lymphatic endothelial cells in dilated lymphatic vessels may be one of the characteristics of Gorham–Stout syndrome¹⁵, which is consistent with the pathological findings of our case.

There are no biomarkers for Gorham–Stout syndrome; however, several studies have mentioned miRNAs and serum biomarkers as potential biomarkers ^2,16.

Given the disease's rarity, there are no established treatment guidelines. However, there have been studies of pharmaceutical therapy, surgery, radiotherapy, or combinations above. Interferon, bisphosphonates, calcium salts, and vitamin D; interferon and zoledronic acid; cyclophosphamide and fluorouracil; salmon calcitonin, alendronate sodium, and sirolimus were among the pharmacological therapies employed^3,17. Sirolimus is an inhibitor of the mammalian target of rapamycin (mTOR), which has antiangiogenic properties and prevents the development of chylothorax in Gorham–Stout syndrome patients¹⁸. The chylothorax did not develop after superior vena cava angiography in our case. The reason may be that the contrast agent blocks abnormal lymphatic vessels.

The main manifestations of our patient were chylothorax and bone destruction. After completing many examinations, the etiology was still unknown. The diagnosis was confirmed by thoracoscopy and bone biopsy. Therefore, the possibility of Gorham–Stout syndrome should be ruled out in patients with clinical chylothorax. We cured chylothorax with superior vena cava angiography. However, the effectiveness of superior vena cava angiography still needs further research.

Ethics approval and consent to participate: The study was approved by the Ethics Committee of Zhongshan Hospital of Xiamen University, Xiamen, China. And the participant provided written informed consent.

Consent for publication: Yes.

Availability of data and material: All data generated or analyzed during this study are included in this published article.

Competing interests: The authors declare that they have no conflict of interest.

Funding: This work was supported by the National Natural Science Foundation of China (82170103), Young people training project from Fujian Province Health Bureau (2020GGB057), and Xiamen Medical and Health Guidance Project (3502Z20214ZD1043).

Authors' contributions: Conception and design: P-Y Hong, X-B Zhang, and Y-L Zhao. Collection and assembly of data: M-H Huang and H-Q Zeng. Data analysis and interpretation: X-B Zhang and M-H Huang. Manuscript writing: All authors. Final approval of manuscript: All authors.

Acknowledgments: Not applicable.

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No competing interests reported.

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Gorham-Stout syndrome: a chylothorax disease with massive bony destruction

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