Early Sirolimus Therapy Combined With Sclerotherapy for the Management of Extensive Neonatal Cervicofacial Lymphatic Malformations: Clinical and MR-Volumetric Follow-up in a Series of 10 Patients

Objectives: Extensive cervicofacial lymphatic malformations (ECFLM) can be highly challenging, especially due to mass effect on the upper airways. Our goal is to underline the interest of neonatal institution of sirolimus combined with macro-cyst sclerotherapy in such conditions. Methods: Ten neonates with ECFLM, diagnosed prenatally in 9, were included in this multicentre retrospective study. Sirolimus residual level, complication and long-term outcomes including were evaluated clinically and via magnetic resonance (MR) volumetry. Results: Two over 10 neonates were intubated at birth. All received sirolimus in the neonatal period, with therapeutic levels difficult to obtain due to hepatic immaturity in 7 cases (mean 21 and range [2–54.1]). Side effects were limited to minor biological changes and a higher propension to upper/lower airway infections in 1 and 3 cases, respectively. Eight patients underwent sclerotherapy (mean 2.9 sessions) by direct injection using 19G and/or 25G catheter. MR volumetry showed a mean volume reduction of 79 (63–96) over an average of 16.2 months of MR follow-up. Sirolimus was stopped in 8 patients due to adequate response (n = 5) or recurrent airway infections (n = 3). PIK3CA mosaic mutations were identified in all 7 genotyped cases. Four patients received alpelisib after sirolimus discontinuation, with clinical improvement. Conclusion: Early sirolimus combined with sclerotherapy is effective for neonates with ECFLM, aiding prenatal counseling of such severe cases.