Abstract
Lymphatic vascular malformations are a relatively uncommon medical occurrence,1,2 but, when they occur, the presence of such lesions can have devastating and potentially life-threatening consequences for the affected individuals.3,4 Historically, lymphatic and other vascular anomalies have been a source of unresolved biological questions and clinical frustration, but, thankfully, the pathogenesis of lymphatic vascular malformation is yielding to biomedical investigative efforts and, as a result, treatment options are becoming ever more favorable.
In the current issue of Lymphatic Research and Biology (LR&B), there are two articles that address aspects of this evolving field. In the first, Eady and colleagues have undertaken an investigation of the expression of embryonic stem cell markers in microcystic lymphatic malformation. Their immunohistochemical examination of tissue samples from nine affected individuals confirms the presence of five of these markers—NANOG, OCT4, SOX2, KLF4, and c-MYC—in all examined specimens. In all nine tissue samples, the expression of OCT4, SOX2, NANOG, KLF4, and c-MYC was observed on the endothelium of vessels within the lesion and there was abundant expression of c-MYC and SOX2, also present on the cells within the stroma. The authors confirmed transcriptional activation of all of the embryonic stem cell markers investigated.
The authors' findings suggest the presence of a primitive population on the endothelium of the vessels and the surrounding stroma of these lesions. The majority of the cells possess a progenitor phenotype with a small number of embryonic stem-like constituents.
Explication of the biology of lymphatic malformations is urgently needed. These early novel findings are encouraging, and further exploration of the biology can be predicted to lead to more effective therapeutic interventions.
In a related subject matter, Triana and colleagues have addressed the question of oral sirolimus in the management of neonates with life-threatening upper airway lymphatic malformations. This mTOR inhibitor has shown increasing promise in the pharmacological management of lymphatic and other complex vascular malformations. 5 However, as the authors indicate, the unique pharmacodynamics of sirolimus in nenonates 6 has hampered systematic evaluation of the use of the drug in this challenging patient population. Here, the authors address this rather urgent set of indications through the evaluation of a series of seven neonatal patients who received sirolimus to address cervical lymphatic malformation. Their observations and extended follow-up of their participating patients support the observation that sirolimus therapy is safe and effective. This approach can be considered a first-line consideration in such patients at high risk for respiratory failure.
LR&B is privileged to present the findings of these two investigative groups, both of which add to the future promise of biomedical advances in the approach to the vexing medical problem of lymphatic vascular malformation.