Recent advances in the pathobiology and clinical management of lymphangioleiomyomatosis

Curr Opin Pulm Med. 2018 Sep;24(5):469-476. doi: 10.1097/MCP.0000000000000502.


Purpose of review: Lymphangioleiomyomatosis (LAM) is a rare systemic disease that occurs almost exclusively in women. In the last few years, our understanding of disease pathobiology has improved substantially; in addition, a guideline document has recently been developed that provides recommendations for the diagnosis and clinical management of patients with LAM. Yet, significant gaps in knowledge remain.

Recent findings: Groundbreaking insights into the cellular biochemistry of LAM have led to the reclassification of the disease as a low-grade, destructive, metastasizing neoplasm. In addition, recent data confirm the potential of next-generation sequencing to detect low-prevalence mutations in tuberous sclerosis (TSC) genes in sporadic LAM. A randomized, double-blind, multicentre trial has confirmed the efficacy of sirolimus in stabilizing lung function, improving functional performance and quality of life, and reducing lymphatic manifestations in patients with LAM. Accordingly, recent guidelines issued by the American Thoracic Society and the Japanese Respiratory Society recommend sirolimus treatment for patients with LAM and reduced lung function. Uncertainty remains, however, with regard to patient selection, and timing of initiation, duration and dosing of treatment.

Summary: Significant advances have been made in the diagnosis and clinical management of patients with LAM. However, additional studies are needed to assess long-term safety and efficacy of sirolimus therapy, and to identify predictors of disease behaviour and response to treatment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / therapeutic use*
  • Female
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / physiopathology
  • Lymphangioleiomyomatosis / diagnosis
  • Lymphangioleiomyomatosis / drug therapy*
  • Lymphangioleiomyomatosis / genetics
  • Lymphangioleiomyomatosis / physiopathology
  • Patient Selection
  • Practice Guidelines as Topic
  • Prognosis
  • Sirolimus / administration & dosage
  • Sirolimus / therapeutic use*
  • Tuberous Sclerosis / genetics


  • Antibiotics, Antineoplastic
  • Sirolimus