Serum Vascular Endothelial Growth Factor-D Prospectively Distinguishes Lymphangioleiomyomatosis From Other Diseases

Objectives The majority of women with lymphangioleiomyomatosis (LAM) present with cystic lung disease, and most require lung biopsy for definitive diagnosis. The purpose of this study was to determine the prospective diagnostic usefulness of a serologic test for vascular endothelial growth factor-D (VEGF-D), a lymphangiogenic growth factor. Methods We prospectively measured serum VEGF-D levels by enzyme-linked immunoassay in 48 women presenting with cystic lung disease. Diagnostic test performance was determined from a cohort of 195 women, with tuberous sclerosis complex (TSC), TSC-LAM, sporadic LAM (S-LAM), and other cystic lung diseases in the differential diagnosis, including biopsy-proven or genetically proven pulmonary Langerhans cell histiocytosis, emphysema, Sjogren syndrome, or Birt-Hogg-Dube syndrome. Results Serum VEGF-D levels were significantly greater in S-LAM (median 1,175 [interquartile range (IQR): 780–2,013] pg/mL; n=56) than in other cystic lung diseases (median 281 [IQR 203–351] pg/mL; n=44, P 800 pg/mL, whereas levels were 600 pg/mL was highly associated with a diagnosis of LAM (specificity 97.6%, likelihood ratio 35.2) and values > 800 pg/mL were diagnostically specific. Serum VEGF-D levels were significantly elevated in women with TSC-LAM (median 3,465 [IQR 1,970–7,195] pg/mL) compared with women with TSC only (median 370 [IQR 291–520] pg/mL), P Conclusions A serum VEGF-D level of > 800 pg/mL in a woman with typical cystic changes on high-resolution CT (HRCT) scan is diagnostically specific for S-LAM and identifies LAM in women with TSC. A negative VEGF-D result does not exclude the diagnosis of LAM. The usefulness of serum VEGF-D testing in men or in women who do not have cystic lung disease on HRCT scan is unknown.