Vascular Endothelial Growth Factor D

Pulmonary cysts are characteristic of different diseases that include, but are not limited to, Langerhans cell histiocytosis, lymphangioleiomyomatosis (LAM), and Birt-Hogg-Dubé syndrome. Vascular endothelial growth factor type D (VEGF-D) is elevated in the plasma of some patients with cystic lung disease. Measurement of serum VEGF-D is a noninvasive test that assist in the differential diagnosis cystic lung disease. 

VEGF is an angiogenic growth factor that is usually produced by malignant cells. VEGF-D is a ligand for lymphatic growth factor VEGF receptors 2 and 3 (VEGFR-2 and VEGFR-3).  Activation of VEGFR-3 can promote lymphatic formation and spread of malignant tumor cells through the lymphatic system to the lymph nodes.

Serum VEGF-D is elevated in patients with LAM compared with healthy controls and patients with other forms of cystic lung disease and emphysema. VEGF-D levels inversely correlate with pulmonary function testing.  A serum VEGF-D cutoff of greater than 800 pg/mL has a sensitivity of 73% and a specificity of 100% for LAM in patients with CT confirmed cystic lung disease. However, a VEGF-D level less than or equal to 800 pg/mL does not rule out a diagnosis of LAM. 

Guidelines by the American Thoracic Society/Japanese Respiratory Society recommend that serum VEGF-D be measured in patients with cystic lung disease suggestive of LAM who have no other clinical or radiological confirmatory features besides lung cysts before proceeding with lung biopsy. They recommend that a threshold of greater than 800 pg/mL to be used to diagnose LAM.  

Treatment of these patients with sirolimus causes a sustained reduction in VEGF-D level.

VEGF-D is measured by enzyme-linked immunoassay. Reference range is 0-600 pg/mL. Specimen requirement is a red-top gel barrier tube of blood. 

References

Ataya A, Riley L and Brantly ML, Serum vascular endothelial growth factor D in cystic lung disease. JAMA 2019;321:401-402. 

McCormackFX, GuptaN, FinlayGR, et al. Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guidelines: lymphangioleiomyomatosis diagnosis and management. Am J Respir Crit Care Med. 2016;194 (6):748-761.