A40-41 Sporadic LAM in a Postmenopausal Woman on Everolimus for Meningioma, a Diagnostic Dilemma

Abstract Introduction Lymphangioleiomyomatosis (LAM) is a rare neoplasm of smooth-muscle-like cells that produces diffuse, thin-walled pulmonary cysts. Serum VEGF-D ≥800 pg/mL with typical HRCT often obviates tissue confirmation. mTOR inhibitors can reduce VEGF-D and yield indeterminate values, creating a diagnostic dilemma in otherwise classic presentations. Case A 54-year-old non-smoking woman with cavernous-sinus meningioma on everolimus (10 mg daily for ∼1 year), rheumatoid arthritis on methotrexate, and prior pulmonary embolism on apixaban presented with hypotension, epistaxis, and hemoptysis. She reported chronic, mild exertional dyspnea. CT chest/abdomen/pelvis showed multiple, bilateral, thinwalled cysts diffusely distributed (figure 1). The patient had no features of tuberous sclerosis complex, no renal angiomyolipomas, and no chylous effusions or lymphangioleiomyomas. Workup for mimics (including alpha-1 antitrypsin deficiency, paraproteinemias, autoimmune serologies, and hypersensitivity panels) was negative. Spirometry at clinical baseline showed FVC 64% and FEV1 67% predicted, FEV1/FVC 84, and DLCO 58%. Serum VEGF-D measured 610 pg/mL while on everolimus. Everolimus and methotrexate were held for pancytopenia/hypoproliferative anemia; apixaban was discontinued. Given classic HRCT findings in a woman, comprehensive exclusion of alternatives, and recognition that mTOR therapy suppresses VEGFD, a working diagnosis of sporadic LAM was made without lung biopsy to avoid procedural risk in diffusely cystic lungs. Discussion This case underscores a practical pitfall: sub-threshold VEGF-D does not exclude LAM when obtained during mTOR therapy. Everolimus can lower VEGF-D substantially, by about 45% in clinical trials, potentially shifting a truly diagnostic value into the indeterminate range (600-800). In such contexts, a guideline-concordant diagnosis can rest on typical HRCT plus clinical features after systematic exclusion of mimics, reserving tissue confirmation for scenarios where histology would change management. Imaging did not suggest Birt-Hogg-Dubé (BHD): cysts in BHD are typically fewer, larger, irregular or lentiform, with basal, medial, and subpleural predominance and costophrenic sparing, often accompanying fibrofolliculomas or renal tumors. In contrast, our patient’s CT demonstrated numerous, uniform, thin-walled cysts diffusely distributed without the characteristic basilar/subpleural clustering or extrapulmonary stigmata of BHD. Integrating biomarker biology, imaging pattern, and treatment context helped avoid an unnecessary invasive biopsy. This abstract is funded by: None