MR lymphangiography of lymphatic abnormalities in children and adults with Noonan syndrome

Abstract

Noonan syndrome is associated with complex lymphatic abnormalities. We report dynamic-contrast enhanced MR lymphangiography (DCMRL) findings in children and adults with Noonan syndrome to further elucidate this complex disease spectrum. A retrospective evaluation of patients with confirmed Noonan syndrome and clinical signs of lymphatic dysfunction undergoing DCMRL between 01/2019 and 04/2021 was performed. MRL included T2-weighted imaging (T2w) and DCMRL. Clinical history/presentation and genetic variants were recorded. T2w-imaging was evaluated for central lymphatic abnormalities and edema distribution. DCMRL was evaluated regarding the presence of cisterna chyli/thoracic duct, lymphatic leakages, pathological lymphatic reflux and abnormal lymphatic perfusion. The time from start of contrast-injection to initial enhancement of the thoracic duct venous junction was measured to calculate the speed of contrast propagation. Eleven patients with Noonan syndrome with lymphatic abnormalities (5 female, 6 male; 7 infants, 4 adults; mean age 10.8 ± 16.4 years) were identified (PTPN11 n = 5/11 [45.5%], RIT1 n = 5/11 [45.5%], KRAS n = 1/11 [9%]). Patients had a chylothorax (n = 10/11 [91%]) and/or pulmonary lymphangiectasia [dilated pulmonary lymph vessels] (n = 9/11 [82%]). Mediastinal/pulmonary edema was depicted in 9/11 (82%) patients. The thoracic duct (TD) was (partially) absent in 10/11 (91%) cases. DCMRL showed lymphatic reflux into intercostal (n = 11/11 [100%]), mediastinal (n = 9/11 [82%]), peribronchial (n = 8/11 [73%]), peripheral (n = 5/11 [45.5%]) and genital lymphatics (n = 4/11 [36%]). Abnormal pulmonary/pleural lymphatic perfusion was seen in 8/11 patients (73%). At infancy peripheral/genital edema was more prevalent in patients with RIT1 than PTPN11 (n = 3/5 vs. n = 0/5). Compared to patients with PTPN11 who had fast lymphatic enhancement in 4/5 patients, enhancement took markedly longer in 4/5 patients with RIT1-mutations. Thoracic duct dysplasia, intercostal reflux and pulmonary/pleural lymphatic perfusion are characteristic findings in patients with Noonan syndrome presenting with chylothorax and/or pulmonary lymphangiectasia. Central lymphatic flow abnormalities show possible phenotypical differences between PTPN11 and RIT1-mutations.

Figure 1

Two-month-old boy with Noonan syndrome-associated bilateral chylothorax and pulmonary lymphangiectasia. (A) Coronal, T2-weighted, non-contrast imaging demonstrates the right-sided course of the thoracic duct from the cisterna chyli (arrow) into the middle part of the thorax where it can no longer be distinguished from surrounding edema. Observe also the extensive pulmonary abnormalities and bilateral pleural effusions. (B) Coronal maximum-intensity projection (MIP) of a contrast-enhanced MR-lymphangiogram demonstrating dilated retroperitoneal lymphatics, the dilated cisterna chyli and thoracic duct in the lower and middle part of the thorax. The thoracic duct runs entirely on the right side and is only rudimentary in the upper part of the thorax. There is also cross-flow through mediastinal lymphatics to the left venous junction. There is only faint enhancement of cervical lymphatics without a discernable TD-venous junction of the thoracic duct. Observe also faint reflux into bilateral intercostal lymphatics and peribronchial lymphatics on the right.

Figure 2

Three-month-old girl with severe pulmonary lymphangiectasia and bilateral Chylothorax. (A–D) Sequential dynamic maximum-intensity projection (MIP) images of coronal contrast-enhanced MR-lymphangiograms showing thoracic duct aplasia in the thorax with massive lymphatic reflux into both lungs. There is collateral flow through peribronchial, diaphragmatic and pleural / intercostal lymphatics and ultimately drainage towards the left venous junction with delayed enhancement of blood vessels.

Figure 3

Six-month-old girl with bilateral chylothorax and pulmonary lymphangiectasia. (A–F) Sequential dynamic maximum-intensity projection (MIP) images of coronal contrast-enhanced MR-lymphangiograms demonstrating fast enhancement of retroperitoneal lymphatics and the thoracic duct. A TD-venous junction is not visible. Instead, the entire lymph flow from the thoracic duct drains into the left bronchiomediastinal trunk with massive reflux into mediastinal and peribronchial lymphatics. Observe also massive reflux into pleural / intercostal lymphatics (left more than right).

Figure 4

50-year-old woman with peripheral/genital edema and chylocolporrhea. (A) Right-anterior oblique, (B) anterior–posterior, (C) left-anterior oblique MIP reconstructions of contrast-enhanced MR-lymphangiograms demonstrating a thin, but continuous thoracic duct with termination in the left venous junction. There is bilateral lymphatic reflux into intercostal lymphatics.

Figure 5

19-year-old male with peripheral/genital edema and chylothorax. Coronal contrast-enhanced MR-lymphangiogram of the inguinal region showing extensive lymphatic reflux from the inguinal nodal injection sites into superficial lymphatics of both legs, of the abdominal wall as well as into genital lymphatics.

Figure 6

Two-month-old girl with chylothorax and pulmonary lymphangiectasia. (A) Anterior–posterior and (B) lateral MIP of contrast-enhanced lymphangiograms demonstrating absence of the thoracic duct in the middle and upper part of the thorax with lymphatic reflux into intercostal/pleural lymphatics, mediastinal as well as peribronchial lymphatics. Observe enhancement of the internal mammary trunks as well as lymphatics along the oesophagus.

Figure 7

Overview of major imaging findings on DCMRL (image: smart.servier.com).

Figure 8

Correlation of current symptoms and major imaging findings (statistical results of Pearson’s correlation).