Lymphangioleiomyomatosis

Definition

Pulmonary disease of women of reproductive age characterized by growth of nodules of modified smooth muscle cells and lymphatics

Clinical
- May be sporadic or associated with tuberous sclerosis complex (TSC)
- Virtually restricted to women of child bearing age
  - Rare males and children affected in TSC kindreds
  - Present in 30% of females with TSC
- Presents with dyspnea, pneumothorax, chylous effusions
- May have associated renal angiomyolipoma (>50%) and meningioma
- Prolonged course but poor prognosis unless transplanted
HRCT
- Cysts scattered diffusely throughout the lung
  - Most are 2-5 mm, occasionally up to 30 mm
Histopathology
- Diagnosis can be made without tissue confirmation if clinical history and radiology are appropriate
- Multifocal nodules of modified smooth muscle cells
  - Slightly increased cytoplasm
    - May have "shredded" appearance (not uniform and dense)
  - Smooth muscle actin and desmin strong positive
  - HMB45 positive but frequently focal or faint
  - May involve interstitium, walls of bronchi and arteries
- Lymph vascular proliferation
  - May be slit-like within muscle nodules or may be dilated
- Cysts form from obstructed airways
  - Thin walled except where involved by nodules of modified muscle cells
- May be seen in transplanted lung but generally not significant clinically
- LAM is a neoplasm in spite of its bland appearance
  - Mutations in TSC1 or 2 in familial cases
  - Mutations in TSC2 in sporadic cases

Gerald J Berry MD
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting/updates: 11/20/10