Approaches to Diagnosis and Management of Congenital Lymphatic Anomalies

Problematic chylous leaks must be imaged to understand the anatomy and physiology of the leak. T2-weighted MRI can be used to identify abnormal lymphatic tissue. Dynamic contrast-­enhanced MR and intranodal lymphangiography provides greater anatomical detail [2, 6]. Thoracic duct cannulation and lymphangiography are useful methods for identifying the source of the leak, and for transthoracic duct delivery of lipiodol, glues, and coils to obstruct fow [20]. Thoracic duct cannulation also provides opportunities to obtain axial lymphatic system samples for research. Caution should be exercised when considering biopsy of lymphatic lesions, since persistent leaks can result. Most of these disor-

ders are caused by somatic mutations, so genetic mutations may only be present in the lesion.

Overview of Complex Lymphatic Anomalies  Multiple disease processes with individual but overlapping pathophysiology and genetics are collectively called complex lymphatic anomalies (CLA) [21]. This array of diseases is believed to stem from embryological errors due to distinct gene mutations [22]. The classi cation of the major CLAs was re ned by the International Society for Study of Vascular Anomalies (ISSVA) in 2018 (https://www.issva.org/classi - cation) and an update incorporating genetic analysis has been recently published [23, 24]. A schematic of some of the mutants known to cause CLAs mapped onto the RAS/MAPK and PI3K/Akt/mTOR pathways is shown in Fig. 21.9.

Fig. 21.9  Signaling pathway mutations implicated in complex lymphatic disorders in adults. Schematic overview of PI3K-AKT and RAS-­MAPK pathways is shown. Disease-causing mutations are shown in blue, potential therapeutic options in red. AKT protein kinase B, ANGPT angiopoietin, CBL casitas B-lineage lymphoma, CCLA central conducting lymphatic disorder, ERK extracellular signal-regulated kinase, GLA generalized lymphatic anomaly, GSD Gorham Stout disease, KLA kaposi-

form lymphangiomatosis, MAPK mitogen-activated protein kinase, MEK mitogen-activated protein kinase kinase, mTORC1 mammalian target of rapamycin complex 1, RAF rapidly accelerated brosarcoma, RAS rat sarcoma, TIE2 tyrosine kinase with immunoglobulin-like and epidermal growth factor homology domains-2, TSC tuberous sclerosis, VEGF vascular endothelial growth factor, VEGFR vascular endothelial growth factor receptor, LEC lymphatic endothelial cell