Should patients with lymphangioleiomyomatosis undergo screening for meningioma?

Pulmonary lymphangioleiomyomatosis (LAM) may be sporadic or associated with tuberous sclerosis complex (TSC). Recently, routine screening for brain abnormalities associated with TSC demonstrated the presence of menin-gioma in 3.2% of patients with LAM (with or without TSC), a prevalence exceeding that expected in the general population [1], thus suggesting that meningiomas may be associated with LAM or its treatment. Indeed, most patients diagnosed with meningioma (seven out of eight) had received hormone replacement therapy and/or progesterone. Hitherto reported cases of meningiomas associated with LAM were mostly asymptomatic [1], with ensuing controversy about the usefulness of systematic brain imaging in patients with LAM [2]. We report the occurrence of symptomatic meningiomas requiring surgery in a patient who had received progesterone therapy for 17 yrs for pulmonary LAM. A female born in 1946 was diagnosed in 1985 with pulmonary LAM, with dyspnoea on exertion, occasional chylopty-sis, and characteristic diffuse cystic lesions on chest computed tomography (CT). Spirometry was normal, carbon dioxide diffusing capacity of the lung was 54% predicted, and resting arterial oxygen tension was 9.3 kPa. The patient had no criteria of TSC. Brain CT was not performed. The diagnosis of LAM was established by open lung biopsy. Immunohis-tochemical studies showed expression of progesterone (but not oestrogen) receptors by LAM cells. Serum levels of oestrogens and progesterone were normal. Therapy with progestative drugs was started, with i.m. medroxyprogester-one 500 mg monthly for 1 yr, then oral nomegestrol 10 mg q.d. Follow-up showed slow impairment of pulmonary function. Oxygen therapy was started in October 2003. The patient was admitted in December 2003 because of behavioural changes, gait disturbances, and bladder and bowel incontinence. Examination revealed major astasia, symmetric brisk reflexes, apragmatism, and decrease in attention and verbal fluency. Cerebral CT showed a right fronto-temporal tumour, 7 cm in diameter (fig. 1), with peritumoural oedema, together with a smaller parasagittal lesion, both suggestive of meningiomas. Surgical resection of the fronto-temporal mass resulted in rapid and complete recovery of the neurological and cognitive status. Histological examination of the tumour showed meningothelial meningioma, with expression of progesterone (but not oestrogen) receptors by tumour cells. Since LAM occurs mainly in females of childbearing age, a role of oestrogens in the progression of pulmonary LAM has been suspected. Progesterone treatment is therefore commonly prescribed, despite lack of evidence of beneficial effect. Both in vitro models and epidemiological studies suggest that female sex hormones may increase the risk …