Novel molecular pathways in Gorham disease: Implications for treatment

Abstract

Rapid advances in evidence-based treatment schedules are a hallmark of modern oncology. In rare neoplastic diseases, however, clinical expertise is hard to build and evidence based on randomized trials almost impossible to conduct. Gorham disease is a rare form of lymphatic proliferation accompanied by osteolysis, which usually occurs in young adults. Despite the fact that the clinical course of Gorham disease is often devastating and occasionally fatal, insights into its biological background are sparse and standardized treatment unavailable. Interestingly, recent knowledge on the mechanisms of lymphangiogenesis may help elucidate the pathophysiology of Gorham disease and lead to novel treatment targets. Here, we discuss our current understanding of Gorham disease, discuss established and emerging therapeutic strategies, and attempt to frame a treatment rationale.

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

“…Several case reports have described the successful use of radiotherapy, achieving pain relief and arresting the spread of osteolysis. Positive results have been achieved with a total dose of 30–45 Gy …”

“…In patients with multifocal lesions, therapeutic options are palliative, and therapy is often aimed at reducing symptoms associated with bone lesions and chylous effusions. [11] Management of chylothorax is often the primary concern. Thoracentesis and pleural drainage are used to treat chylothorax to relieve respiratory distress.…”

“…Positive results have been achieved with a total dose of 30-45 Gy. [11] Patients with osteolysis have been treated with drugs that inhibit bone resorption, including bisphosphonates such as pamidronic or zoledronic acid. [12] Patients with bone or thoracic lesions have been treated with interferon-α-2b, which inhibits the formation of lymphatic vessels.…”

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

“…Several agents with anti‐angiogenic properties have been used with varying degrees of success. These agents includes interferon alfa, bevacizumab, propranolol and thalidomide . Octreotide, which can reduce thoracic duct flow, has been used in many lymphatic vascular diseases, including GSD .…”

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

“…The growth factors VEGF-A and VEGF-C, but also plateletderived growth factor-BB, play a role in the invasion of lymphatic vessels (26). These growth factors signal through the same pathway which ends in the mammalian target of rapamycin (mTor) (27)(28)(29). mTor is an important kinase in the progression of the cell cycle and a key regulator of immune responses.…”