Rare Lung Disease

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General Information about Rare Lung Disease


Generalized lymphatic anomaly (GLA), also known as lymphangiomatosis, is a rare condition in which the lymphatic vessels proliferate abnormally in some areas of the body. [1-3] It can develop in virtually all organs, including the brain, lung, heart, liver, spleen, and bones.[1,4] Congenital abnormalities in the developing lymphatic system are thought to play a major role in pathogenesis of the condition, with lymphatic cysts and dilation continuing to progress after birth. The condition tends to present before age 20, and approximately three-quarters of patients have involvement of more than one organ. [5] Many symptoms are due to compression of tissues by dilated lymphatic channels or by the accumulation of lymph and chyle in structures such as the pleura (chylothorax), pericardium (chylopericardium), or abdominal cavity (chyloascites.)  Chylothorax can be either unilateral or bilateral. [6]

Gorham-Stout disease (GSD) is related to GLA; lymphatic proliferation occurs predominantly in the bones, producing cortical bone loss and progressive bony resorption. Patients may present with bone pain, weakness, or pathological fractures. The shoulder, skull, and pelvic girdle are most commonly affected. [5]

GLA and GSD were first described in the 19th century, but because of their rarity, understanding of the conditions remains limited nearly two centuries after their initial description. It is still not entirely clear if GLA and GSD represent the same underlying disorder, with GSD more prominently affecting bones, or whether there are unique aspects in their pathophysiology. [1,6]

The terminology of these conditions can be challenging to patients and practitioners alike:

  • A number of synonyms of GSD have been used, including vanishing bone disease, phantom bone disease, disappearing bone disease, Gorham’s disease, Gorham-Stout syndrome, massive osteolysis, and acute spontaneous absorption of bone.

  • GLA has also been referred to as lymphangiomatosis, generalized cystic lymphangiomatosis, or cystic angiomatosis. A number of other conditions have similar names but are not related to GLA, such as pulmonary lymphangioleiomyomatosis (LAM), lymphangiectasis, and pulmonary capillary hemangiomatosis.

GLA and GSD are sporadic and nonhereditary. The culprit molecular mechanisms remain unclear, although a role for disordered regulation by vascular endothelial growth factor has been hypothesized. [7] Pulmonary manifestations of GLA and GSD can include shortness of breath, wheezing, and cough, as well as findings consistent with pleural effusion, pericardial effusion, lower lobe interstitial lung disease, or lesions of bones in the scapula, ribs or thoracic vertebrae.

There are no standardized treatments for GLA and GSD. External beam radiation therapy, surgical therapy, interferon alpha-2b, lung transplantation, and bisphosphonates have been employed but none have been validated in controlled trials. Ligation of the thoracic duct, with or without concomitant pleurodesis may be required to manage chylothorax. [5, 8]


  1. Lala S, Mulliken JB, Alomari AI, Fishman SJ, Kozakewich HP, Chaudry G. Gorham-Stout disease and generalized lymphatic anomaly--clinical, radiologic, and histologic differentiation. Skeletal Radiol. 2013 Jul;42(7):917-24.

  2. Blei F. Lymphangiomatosis: clinical overview. Lymphat Res Biol. 2011;9(4):185-90.

  3. Tazelaar HD, Kerr D, Yousem SA, Saldana MJ, Langston C, Colby TV. Diffuse pulmonary lymphangiomatosis. Hum Pathol. 1993 Dec;24(12):1313-22.

  4. Satria MN, Pacheco-Rodriguez G, Moss J. Pulmonary lymphangiomatosis. Lymphat Res Biol. 2011;9(4):191-3.

  5. Hu P, Yuan XG, Hu XY, Shen FR, Wang JA. Gorham-Stout syndrome in mainland China: a case series of 67 patients and review of the literature. J Zhejiang Univ Sci B. 2013 Aug;14(8):729-35.

  6. Venkatramani R, Ma NS, Pitukcheewanont P, Malogolowkin MH, Mascarenhas L. Gorham's disease and diffuse lymphangiomatosis in children and adolescents. Pediatr Blood Cancer. 2011 Apr;56(4):667-70.

  7. Dupond JL, Bermont L, Runge M, de Billy M. Plasma VEGF determination in disseminated lymphangiomatosis-Gorham-Stout syndrome: a marker of activity? A case report with a 5-year follow-up. Bone. 2010 Mar;46(3):873-6.

  8. Kinnier CV, Eu JP, Davis RD, Howell DN, Sheets J, Palmer SM. Successful bilateral lung transplantation for lymphangiomatosis. Am J Transplant. 2008 Sep;8(9):1946-50

Four Facts About Lymphangiomatosis & Gorham’s Disease
  1. Lymphangiomatosis and Gorham’s disease are thought to be a spectrum of disease:

    • Lymphangiomatosis, recently classified as generalized lymphatic anomaly (GLA) is marked by the presence of cysts that result from an increase both in the size and number of thin-walled lymphatic channels that are abnormally interconnected and dilated

    • Gorham’s disease (recently classified as Gorham-Stout disease) - it is believed results from a derangement of osteoclast activity that is always accompanied by vascular anomaly (often lymphatic in origin and having the same features characteristic of lymphangiomatosis) that may extend into the soft tissues, particularly in the chest. 

  2. When it involves the lungs, lymphangiomatosis or Gorham-Stout causes chylothorax, chylopericardium, and interstitial disease that result in chronic respiratory failure. 

  3. Affects males and females of all ethnicities equally and most commonly presents itself by age 20 years

  4. Pulmonary lymphangiomatosis is separate and distinct from lymphangiectasis, lymphangioleiomyomatosis (LAM), pulmonary capillary hemangiomatosis, Kaposi’s sarcoma, and kaposiform hemangioendothelioma.