TABLE 1

Relevant features in tuberous sclerosis complex (TSC)-associated lymphangioleiomyomatosis (LAM) compared to sporadic lymphangioleiomyomatosis (S-LAM)

TSC-LAMS-LAM
Genetics
  • Both TSC1 and TSC2 germinal mutations

  • TSC2 mutations more prevalent

  • Somatic TSC2 mutations in affected organs: lung with LAM, renal AML (TSC1 mutations extremely rare)

Epidemiology
  • Younger age at diagnosis

  • Reported in males (virtually asymptomatic)

  • Young to middle-aged females

  • Exclusively in females

Clinical presentation
  • Less symptomatic

  • Spontaneous pneumothorax more frequent

  • Systematic screening in TSC patients

  • Shortness of breath

  • Spontaneous pneumothorax

  • Incidental cysts on imaging

Imaging
  • Milder cystic lung disease

  • Coexistence of MMPH

  • Hepatic and renal AMLs (especially bilateral) more common

  • Extrathoracic TSC features

  • Greater extent of lung cysts

  • Normal underlying pulmonary parenchyma

  • Lymphangioleiomyomas and chylothorax more frequent

Lung physiology
  • Normal lung function more frequent

  • Airflow obstruction and diffusion abnormalities possible

  • Airflow obstruction and diffusion abnormalities more frequent

  • Normal lung function possible

Serum VEGF-D
  • Elevated (>800 pg·mL−1) in >95% of patients

  • Higher serum concentrations

  • Elevated (>800 pg·mL−1) in 60–70% of patients

Indications for mTOR inhibitors
  • For pulmonary LAM: same indications as in S-LAM

  • May be indicated for extrathoracic manifestations of TSC

  • For patients with LAM with abnormal/declining lung function

  • For selected patients with LAM with problematic chylous effusions

Prognosis
  • Generally milder disease

  • Lung transplantation more frequent

VEGF: vascular endothelial growth factor; mTOR: mammalian target of rapamycin; AML: angiomyolipoma; MMPH: multifocal micronodular pneumocyte hyperplasia.