Serum vascular endothelial growth factor-D prospectively distinguishes lymphangioleiomyomatosis from other diseases.
OBJECTIVE
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, Sjögren syndrome, or Birt-Hogg-Dubé 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 < .001). In the cohort evaluated prospectively, 12 of the 15 individuals ultimately diagnosed with LAM by biopsy had VEGF-D levels of > 800 pg/mL, whereas levels were < 600 pg/mL in all 18 subjects later diagnosed with other causes of cystic lung disease. Receiver operating characteristic curves demonstrated that VEGF-D effectively identified LAM, with an area under the curve of 0.961(95% CI, 0.923-0.992). A VEGF-D level of > 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 < .001).


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.
Young
Lisa R
LR
Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Vandyke
Rhonda
R
Gulleman
Peter M
PM
Inoue
Yoshikazu
Y
Brown
Kevin K
KK
Schmidt
Laura S
LS
Linehan
W Marston
WM
Hajjar
Fuad
F
Kinder
Brent W
BW
Trapnell
Bruce C
BC
Bissler
John J
JJ
Franz
David N
DN
McCormack
Francis X
FX
D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008171:Lung Diseases / Q000097:blood* / Q000473:pathology*; D018192:Lymphangioleiomyomatosis / Q000097:blood* / Q000175:diagnosis*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D015203:Reproducibility of Results; D042643:Vascular Endothelial Growth Factor D / Q000097:blood*; D055815:Young Adult
D014408:Biomarkers, Tumor; D042643:Vascular Endothelial Growth Factor D
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