Role of Hormonal Manipulations in Delaying the Progression of Lymphangioleiomyomatosis (LAM): A 16-Years Follow-Up Report after Oophorectomy

Abstract

Introduction: Lymphangioleiomyomatosis (LAM) is a slowly progressive lung disease that leads to respiratory failure over one to two decades. It is exclusively seen in women and is characterized by progressive proliferation of smooth muscle-like cells (LAM cells) in lung parenchyma and causes cystic destruction, chylous pleural effusions and recurrent pneumothoraces. LAM has historically been considered an estrogen dependent tumor and was treated with hormonal manipulation strategies such as antiestrogens, antiprogesterones and oophorectomy. Current insights into the pathophysiology of LAM have provided new treatment drugs such as sirolimus, a mTOR inhibitor, that is effective in stabilizing lung function. Since the advent of novel therapies, hormonal manipulation strategies have become less popular. We describe a case of LAM in a young woman who underwent oophorectomy and was followed closely for 16 years without worsening of her lung function. PRESENTATION: A 49-year-old female was referred to our institution in 1996 for recurrent pneumothoraces. Computed tomography of the chest demonstrated (Fig 1) numerous cystic lesions uniformly scattered throughout the lung. A subsequent lung biopsy confirmed the histologic diagnosis of LAM (Fig 2). Pulmonary function tests showed FEV1 of 2.68 L, FVC of 4.56 L, TLC of 6.18 L and a DLCO of 21.3. She had a 15 years history of smoking and her other comorbidities included asthma and uterine leiomyoma. She was subsequently treated with hysterectomy and oophorectomy. Sixteen years following the surgery, she remained asymptomatic and serial PFTs done over the same time period interestingly did not show progressive worsening of her lung function. Her most recent PFTs in 2013 showed FEV1 of 2.25 L. She did not receive any targeted therapy and is not requiring supplemental oxygen at rest or during exertion. DISCUSSION: LAM is a rare multisystem disease of women that targets the lung. There are several features of LAM that suggests its estrogen dependency such as its propensity to affect females, occurrence before menopause, and worsening respiratory function during pregnancy. Estrogen and progesterone receptors expression is seen in LAM cells. Although novel agents have shown promise in controlling symptoms, they are associated with drug toxicity and development of resistance, and never been tested in RCTs in direct comparison with hormonal manipulation. In this report we hope to demonstrate that oophorectomy might still be beneficial in certain subset of patients with LAM.