Abstract Introduction Lymphangioleiomyomatosis (LAM) is a multisystem disorder subdivided into two clinical variants: tuberous sclerosis (TSC)-associated and sporadic, with the latter affecting females exclusively. Pre-menopausal women are disproportionately affected, with the lung being the most common site of involvement. Clinical data suggest that menstruation, pregnancy, and exogenous hormone therapy can lead to worsening of symptoms associated with LAM. Case Description A 40-year-old female with a medical history significant for stage 1 endometrial cancer on medroxyprogesterone presented to the emergency department with complaints of pleuritic, left-sided chest pain for two weeks. The patient was a nonsmoker with no prior history of pulmonary disease. Chest x-ray demonstrated a small left-sided pneumothorax. The CT chest scan revealed numerous small, simple cysts diffusely present in both lungs, without the presence of nodules or fibrosis. The patient was referred to thoracic surgery and underwent left thoracoscopy with blebectomy and talc pleurodesis. Surgical lung biopsy demonstrated lung parenchyma showing emphysematous changes and scattered small cysts associated with proliferation of small muscle bundles, consistent with LAM. The muscle bundles were immunopositive for HMB-45, smooth muscle actin (SMA), and estrogen receptors (ER). The pneumothorax resolved after surgery, and the patient was discharged to outpatient care. Discussion Estrogen has a significant impact on the progression and severity of sporadic LAM. The hormone directly affects the proliferation and migration of LAM cells by acting on ER on abnormal smooth muscle, and indirectly via complex pathways involving mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK). Rise in estrogen during pregnancy has been correlated with the development of LAM and a higher incidence of complications such as pneumothorax, preterm labor, and miscarriage. Similarly, fluctuations in estrogen and progesterone during the menstrual cycle can impact LAM progression. The use of estrogen contraceptives has been associated with an earlier onset of LAM. Endometrial cancer remains a clear risk factor for the development of LAM, due to the common risk of prolonged and/or elevated exposure to estrogen. Both are linked to dysregulation of the mTOR signaling pathway, evidenced by mTOR inhibitors as an emerging therapy for endometrial cancer. The impact of progesterone on LAM is not well understood. Older retrospective data support the role of medroxyprogesterone in the treatment of LAM; however, recent data do not support this. Non-uniform expression of progesterone receptors on LAM cells may explain the variable effects of progesterone on disease progression. This abstract is funded by: None
Bakhru et al. (Fri,) studied this question.