Lymphangioleiomyomatosis (LAM) is a cystic lung disease that predominantly affects women. Roughly 90% of cases are sporadic and are caused by somatic mutation of the TSC2 gene, but some patients develop LAM as part of the syndrome Tuberous Sclerosis Complex (TSC), which is caused by germline mutations either TSC1 or TSC2.
Angiomyolipoma (AML) is a type of kidney tumour that develops in nearly 100% of patients with TSC, and 50% of patients with sporadic LAM. AML are typically benign, but if untreated, larger tumours can haemorrhage and require the patient to undergo a nephrectomy. While the natural history of AML is known for TSC patients, it has not been systematically studied in LAM patients, and there are no official clinical recommendations of how to monitor and treat AML in sporadic LAM patients.
Yeoh et al. (2014) recently published a natural history study on a cohort of 107 sporadic LAM patients recruited via the National Centre for LAM in Nottingham, UK. Of these patients, 53 (50%) had had at least 1 AML in their lifetime and the average age of AML diagnosis was 39.1. Ten patients were diagnosed with AML up to 11 years before they were diagnosed with LAM, ten patients were diagnosed with both at the same time, and the remaining patients were diagnosed with AML up to 38 years after their LAM diagnosis. This suggests that sporadic LAM patients are at risk of developing AML throughout their entire lifetime.
Presence of AML was not linked to the severity of the pulmonary symptoms of LAM in these patients. AMLs in sporadic LAM patients were generally smaller, less likely to be bilateral, and the time from diagnosis to renal event – such as haemorrhage or surgical intervention – was 34 years, compared with 25 years in TSC patients. However, there was no difference in the incidence of haemorrhage or the need for medical intervention between this cohort and TSC patients. This suggests that AML in sporadic LAM patients should be managed in a similar fashion to AML in TSC patients.
The authors recommend that abdominal MRI should be performed every 1 to 3 years throughout the lifetime of sporadic LAM patients, and surgical intervention should occur when tumours reach 3 cm, as patients with larger tumours are at significant risk of haemorrhaging. All patients should have an abdominal MRI scan when they are diagnosed with LAM to assess whether they have any AMLs. Patients with tumours smaller than 1 cm in diameter should have follow up scans every two years, patients with tumours between 1-2cm in diameter should be screened annually, and patients with tumours over 3 cm should either have follow up scans after 6 months, or should be referred for intervention.
The authors note that this study only takes tumour size into account and suggest that contrast CT or MRI could be used to detect the vasculature of AML tumours, which may allow patients to be stratified into high risk and low risk groups that are managed differently. Indeed, there were 11 patients in this cohort who underwent nephrectomy to treat AML haemorrhage, and the average age of these patients at the time of surgery was 23. This is significantly younger than the average age of AML diagnosis of the cohort as a whole, which was 39.1, and suggests that these 11 patients did have a more aggressive form of AML.
- Yeoh ZW, Navaratnam V, Bhatt R, McCafferty I, Hubbard RB, & Johnson SR (2014). Natural history of angiomyolipoma in lymphangioleiomyomatosis: implications for screening and surveillance. Orphanet journal of rare diseases, 9 PMID: 25277108