Lymphangioleiomyomatosis

#med #disease #onc #pulm

Presentation :

Presenting symptoms: Progressive dyspnea and fatigue (66%), spontaneous pneumothorax (33%), pleural effusion (25%).
- Acute respiratory failure can manifest during pregnancy or after the use of oral estrogen as a result of hyperestrogenism.
- May also present with productive cough, wheezing, chest pain, pulmonary hypertension, or hemoptysis.
Can occur sporadically (nearly exclusively in premenopausal women) or associated with Tuberous Sclerosis
Highly associated with Renal Angiomyolipomas

Abnormal growth of atypical smooth muscle cells in the lung vasculature, lymphatics, and alveoli that leads to the formation of diffuse cysts in the lungs
Disease is exacerbated by estrogen suggestive of a hormonal component
Associated with mutations to TSC1 (hamartin) or TSC2 (tuberin) leading to loss of inhibition of mTOR

Per ATS guidelines clinical diagnosis established (without need for biopsy) with positive CT imaging PLUS
- a diagnosis of TSC
- a chylous effusion
- renal angiomyolipoma
- Elevated VEGF-D (>800 pg/ml; sens 73 | spec 99%; this is not as solid and may still require biopsy depending on clinical circumstance)
High-res chest CT (high sens/spec) shows multiple (>10), thin-walled, well-demarcated, diffuse/bilateral pulmonary cysts.
- CXR is non-diagnostic aside from showing non-specific Pneumothorax or Pleural Effusion
- If effusion is present thoracentesis may reveal chylothorax, resulting from lymphatic disruption from tumor growth
- Screening CT is recommended for women with spontaneous pneumothorax during childbearing age, recurrent pneumothorax, or bilateral pneumothorax.
Biopsy via VAT, trans-bronchial, or surgical wedge resection remains the gold standard (albeit not always practical). Histopath reveals abnormal smooth muscle-like cells in the lymphovascular and alveolar tissues.
PFTs can show obstructive patterns, which is sometimes bronchodilator responsive which can lead to misdiagnosis of asthma

The mTOR inhibitor Sirolimus has been shown to slow progression of symptoms, and stabilize PFTs
Bronchodilators have efficacy in those with bronchodilator responsive PFTs
Pulmonary rehab helps improve endurance and QoL
Lung transplantation may be necessary for progresses/refractory symptoms despite sirolimus treatment; however recurrence after transplantation has been described
Pleurodesis can be effecacious for individuals with recurrent Pneumothorax
- Pressure changes associated with air travel, increase risk of pulmonary cyst rupture and pneumothorax; patients should be counseled about air travel-associated risks and the possible need for inflight oxygen
Avoid estrogen OCPs; progesterone OCPs are safe

The median transplant-free survival in patients with LAM is estimated to be 29 years from symptom onset and 23 years from diagnosis