Central conducting lymphatic anomaly: from bench to bedside
Luciana Daniela Garlisi Torales, … , Christopher L. Smith, Sarah E. Sheppard
Luciana Daniela Garlisi Torales, … , Christopher L. Smith, Sarah E. Sheppard
Published April 15, 2024
Citation Information: J Clin Invest. 2024;134(8):e172839. https://doi.org/10.1172/JCI172839.
View: Text | PDF
Review Series Article has an altmetric score of 3

Central conducting lymphatic anomaly: from bench to bedside

Abstract

Central conducting lymphatic anomaly (CCLA) is a complex lymphatic anomaly characterized by abnormalities of the central lymphatics and may present with nonimmune fetal hydrops, chylothorax, chylous ascites, or lymphedema. CCLA has historically been difficult to diagnose and treat; however, recent advances in imaging, such as dynamic contrast magnetic resonance lymphangiography, and in genomics, such as deep sequencing and utilization of cell-free DNA, have improved diagnosis and refined both genotype and phenotype. Furthermore, in vitro and in vivo models have confirmed genetic causes of CCLA, defined the underlying pathogenesis, and facilitated personalized medicine to improve outcomes. Basic, translational, and clinical science are essential for a bedside-to-bench and back approach for CCLA.

Authors

Luciana Daniela Garlisi Torales, Benjamin A. Sempowski, Georgia L. Krikorian, Kristina M. Woodis, Scott M. Paulissen, Christopher L. Smith, Sarah E. Sheppard

×

Figure 2

Schematic of the various DCMRL approaches.

Options: View larger image (or click on image) Download as PowerPoint
Schematic of the various DCMRL approaches. DCMRL can be performed using ...
DCMRL can be performed using contrast that is injected into a lymph node, liver, and/or mesentery. Traditional T2 space MRI and DCMRL imaging representing the typical appearance of the lymphatic vessels (A) compared with their appearance in three individuals with CCLA due to mosaic BRAF (B), Down syndrome (C), and PIEZO1–generalized lymphatic dysplasia (D). In B, mosaic BRAF p.Val600Glu, T2 space imaging shows substantial edema in the intercostal, mesentery, and liver lymphatics that correlates with abnormal perfusion patterns on intrahepatic DCMRL. Also note the abnormal lymphatic thoracic vessels lacking a normal thoracic duct. In C, Down syndrome, T2 space imaging shows edema in the supraclavicular (and superior mediastinal) lymphatics (arrows). On intrahepatic DCMRL, there is retrograde flow into retroperitoneal lymphatics and intercostal, mediastinal, pulmonary, and supraclavicular perfusion (arrows). Arrowhead indicates a patent thoracic duct that courses to the left venous angle. In D, PIEZO1–generalized lymphatic dysplasia, T2 space imaging shows bilateral pleural effusions, and pulmonary and retroperitoneal edema (arrows). Intrahepatic DCMRL shows extensive flow to the hepatic capsular lymphatics, with extension into the mediastinum and pulmonary lymphatics (arrows). There is also retrograde flow into the retroperitoneal lumbar and mesenteric lymphatics. The arrowhead indicates a small thoracic duct coursing to the left venous angle, patent on follow-up imaging. IM, intramesenteric; IH, intrahepatic; IN, intranodal. Images reproduced from ref. 61 with permission.