Lymphangioleiomyomatosis (LAM) is a rare multisystem disease characterised by abnormal proliferation of smooth muscle–like cells within the lungs, lymphatics, vasculature and pleura. It occurs almost exclusively in women and has an estimated prevalence of approximately 1 per million¹.The disease leads to progressive cystic destruction of lung parenchyma, impaired gas exchange and eventual respiratory failure. Clinical presentation is often nonspecific, with exertional dyspnoea being the most common initial symptom. As a result, LAM is frequently misdiagnosed as asthma or chronic obstructive pulmonary disease, delaying definitive diagnosis². High-resolution CT (HRCT) of the chest demonstrating diffuse, thin-walled cysts is central to diagnosis, with histopathology reserved for atypical cases¹. The introduction of mammalian target of rapamycin (mTOR) inhibitors, particularly sirolimus, has transformed management by stabilising lung function and improving quality of life³. However, long-term real-world data remain limited. We present a case of sporadic LAM diagnosed in later adulthood, with sustained clinical and functional stability over 2 years of sirolimus therapy.

A 58-year-old Australian woman, an ex-smoker (3 cigarettes per day for 3 years), presented with progressive exertional dyspnoea over several years. She had been treated as having asthma with maximal inhaler therapy, without symptomatic improvement. There was no history of pneumothorax, haemoptysis, chylous effusions or systemic disease. On examination, the chest was clear with no wheeze or crackles. Oxygen saturation was 97% on room air, and she was not in respiratory distress. Investigations Chest radiography was unremarkable (Figures 1 and 2). HRCT of the chest demonstrated multiple, round, thin-walled cysts of relatively uniform size distributed diffusely throughout both lungs, without zonal predominance (Figures 3–5). Pulmonary function testing revealed preserved spirometry (FEV₁ 92% predicted, FVC 88% predicted, FEV₁/FVC ratio 0.79). Lung volumes were not significantly reduced. However, diffusion capacity was impaired, with DLCO 55% predicted and KCO 50% predicted. During a six-minute walk test, the patient was only able to walk for 2 minutes before termination due to significant desaturation. Oxygen saturation declined from 97% at baseline to a nadir of 88%, with associated tachycardia, consistent with diffusion limitation and impaired exercise tolerance. Thoracoscopy demonstrated smooth pleural surfaces with multiple small blebs and cysts. Thoracoscopic lung biopsy revealed atypical proliferation of smooth muscle–like cells infiltrating the lung parenchyma and interstitium, confirming the diagnosis of lymphangioleiomyomatosis (Figures 10–12). Asthma Chronic obstructive pulmonary disease Pulmonary Langerhans cell histiocytosis Birt–Hogg–Dubé syndrome Lymphoid interstitial pneumonia Treatment The patient was commenced on sirolimus therapy following confirmation of the diagnosis. Treatment was well tolerated, with no significant adverse effects reported. Outcome and follow-up Over a 2-year follow-up period, serial pulmonary function tests demonstrated stabilisation of lung function, with no further decline in FEV₁ or DLCO (Figures 13–16). Clinically, the patient reported improved exercise tolerance and reduced dyspnoea. No disease-related complications occurred during follow-up.

LAM is a rare but important differential diagnosis in women presenting with unexplained dyspnoea, particularly when spirometry is preserved and diffusion capacity is reduced. Although it most commonly affects women of reproductive age, delayed diagnosis into later adulthood is increasingly recognised⁴. Misdiagnosis as asthma is common due to overlapping symptoms and initially preserved airflow⁵.

HRCT findings of diffuse, thin-walled cysts are highly characteristic, and lung biopsy remains valuable when diagnostic uncertainty persists. The pathogenic overlap between sporadic LAM and tuberous sclerosis complex, particularly involving mutations in the TSC2 gene, has led to the successful use of mTOR inhibitors⁶.

The MILES trial demonstrated that sirolimus stabilises lung function and improves quality of life in patients with moderate disease³. Long-term observational studies suggest sustained benefit with acceptable tolerability⁷. This case supports existing evidence that sirolimus can provide durable disease stabilisation, even in older patients and in real-world clinical settings.

Learning points

• Lymphangioleiomyomatosis should be considered in women with unexplained dyspnoea, even in later adulthood.
• Preserved spirometry does not exclude LAM; diffusion impairment and exertional desaturation may be early clues.
• HRCT is central to diagnosis, with lung biopsy reserved for atypical cases.
• Sirolimus is an effective and well-tolerated long-term therapy for stabilising lung function in LAM.

Patient consent for publication: Obtained.

Competing interests: None declared.

Funding: None declared.

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