A 20-year old woman was diagnosed at birth as having TSC. She developed epilepsy at the age of 15 months. Brain magnetic resonance imaging (MRI) revealed a SEGA and cortical tubers. Other typical manifestations that appeared progressively over time included multiple renal AMLs, cardiac rhabdomyoma, facial angiofibromas, hypomelanotic macules and ungueal fibromas. No genetic testing was performed in the patient, but genetic analysis in both parents did not detect any TSC1 or TSC2 mutation.
At the age of 14, the gradual growth of the SEGA led to hydrocephalus, which was treated by ventriculoperitoneal shunting and fenestration of the septum pellucidum. Due to recurrent intracranial hypertension, incomplete surgical removal of the tumor was performed 3 months later, and the diagnosis of SEGA was confirmed at histopathology.
At the age of 15, a growing right renal mass suspect of AML led to selective arterial renal embolization and concomitant needle biopsy. Despite careful histopathological examination and external review, it was not possible to discriminate between epithelioid AML and papillary renal cell carcinoma, and regular imaging follow-up was instituted. A chest high-resolution CT (HRCT) revealed numerous small pulmonary nodules randomly distributed throughout both lungs.
At first visit to our Department, the patient was a non-smoker and had no respiratory symptoms. Lung auscultation was unremarkable. Pulmonary function tests showed normal lung volumes and carbon monoxide transfer coefficient. There was no feature suggesting an infection, including tuberculosis. In the absence of cystic lung lesions on HRCT, LAM was ruled out. Follow-up HRCT at 6, 12 and 18 months showed stability in the number, size and density of all pulmonary nodules, thus reducing the likelihood of metastatic disease and suggesting MMPH. Moreover, the renal mass remained stable for 2 years after embolization, thus reinforcing the hypothesis of AML.
At the age of 18, owing to progressive SEGA growth and increased seizure frequency, the patient was started on everolimus 10 mg daily. The treatment was well tolerated. Brain MRI after 3 months showed a significant reduction in SEGA size, which subsequently remained stable at 8 and 11 months of treatment. A follow-up chest HRCT performed 3 months after everolimus initiation (and 3 years after the first thoracic imaging) showed a remarkable decrease in density of all pulmonary MMPH lesions, without obvious change in size (Fig. 1A-C). We measured the diameter and density of the 8 most easily perceptible solid nodules on the 4 HRCT performed before everolimus, and the last one on everolimus. As shown in Fig. 1D, long and short axis (axial view) of all 8 nodules did not change over time either before or after everolimus therapy. In contrast, the density of all 8 nodules decreased after everolimus initiation, suggesting a therapeutic effect of everolimus on these lesions. Abdominal HRCT at 3 months of treatment also demonstrated a decreased density of all AMLs.