Prevalence of lymphangioleiomyomatosis in an Irish population and biomarker utility

Abstract

Lymphangioleiomyomatosis (LAM) is a low-grade metastasizing neoplasm causing cystic lung disease. Sporadic or associated with tuberous-sclerosis complex (TSC), it predominantly affects pre-menopausal women. Estimated prevalence is 3-8 cases per million. Characteristic HRCT Thorax plus one of; serum VEGF-D ≥800pg/ml, TSC,renal angiomyolipomas (AML), chylous effusions or lymphangioleiomyomas are diagnostic. Data on 30 patients was analysed: age at diagnosis, hormone status, TSC, biopsy history, VEGF-D levels, pneumothorax or chylothorax, AML, PFTs and cyst-burden scores. CT cyst-burden scores were obtained from DICOM images using SyngoVia post processing software. Mean age was 50.8 years (range:32-85 years), 57% pre-menopausal and 23% prescribed mTOR inhibitors. 10% require long term oxygen.70% had VEGF-D levels (mean 626pg/ml, SD +/-599.48).2 patients had TSC-LAM, both had chylothorax, AML and VEGF-D levels>800pg/ml. Of the remaining 28, 21% met criteria with HRCT findings and AML, 4% had AML and VEGF-D levels >800, 4% had chylothorax and 4% had chylothorax and diagnostic VEGF-D levels. The remainder had a tissue diagnosis and/or characteristic CT findings. Mean DLCO was 67.94% (+/-23.42) and FEV1 85.7% (+/-16.05). There was a negative correlation between VEGF-D and DLCO (n=13; R2=0.458; p=0.0111) and VEGF-D and FEV1 (n=14; R2=0.2741, p=0.0547). Mean cyst-burden was 14.6%(+/-15.8) of total lung volume inversely correlating with DLCO (R2=0.79, p=0.01). Thirty cases of LAM represent a prevalence of 12.6 cases/million women. While VEGF-D is a recognised correlate of pulmonary function, cyst scores require longitudinal prospective assessment to determine utility as clinical biomarker.