Congenital pulmonary lymphangiectasia

Abstract

Congenital pulmonary lymphangiectasia (PL) is a rare developmental disorder involving the lung, and characterized by pulmonary subpleural, interlobar, perivascular and peribronchial lymphatic dilatation. The prevalence is unknown. PL presents at birth with severe respiratory distress, tachypnea and cyanosis, with a very high mortality rate at or within a few hours of birth. Most reported cases are sporadic and the etiology is not completely understood. It has been suggested that PL lymphatic channels of the fetal lung do not undergo the normal regression process at 20 weeks of gestation. Secondary PL may be caused by a cardiac lesion. The diagnostic approach includes complete family and obstetric history, conventional radiologic studies, ultrasound and magnetic resonance studies, lymphoscintigraphy, lung functionality tests, lung biopsy, bronchoscopy, and pleural effusion examination. During the prenatal period, all causes leading to hydrops fetalis should be considered in the diagnosis of PL. Fetal ultrasound evaluation plays a key role in the antenatal diagnosis of PL. At birth, mechanical ventilation and pleural drainage are nearly always necessary to obtain a favorable outcome of respiratory distress. Home supplemental oxygen therapy and symptomatic treatment of recurrent cough and wheeze are often necessary during childhood, sometimes associated with prolonged pleural drainage. Recent advances in intensive neonatal care have changed the previously nearly fatal outcome of PL at birth. Patients affected by PL who survive infancy, present medical problems which are characteristic of chronic lung disease.

Figure 1

Molecular pathways in Lymphangiogenesis. The four-step model for lymphatic vasculature formation is summarized in this scheme. Time line of endothelial cell gene expression in lymphangiogenesis refers to the murine lymphatic system. LEC competence is the autonomous ability of venous endothelial cells to respond to an inductive signal. LEC bias is the bias toward LEC determination and is characteristic of LEC precursors; LEC bias is eventually lost in other venous endothelial cells. LEC specification is characterized by initiation of LEC budding; LEC specification occurs when biased endothelial cells differentiate. LEC differentiation is characterized by four different events, as shown in the figure. During this period lymphatic vessel differentiate and maturation occurs in a stepwise manner leading to the syntesis of all of the main lymphatic vessel components to mature lymphatics. LEC: lymphatic endothelial cell. Timing: E means embryonic days. Lyve1: lymphatic vessel endothelial hyaluronan receptor 1. Vegfr3: vascular endothelial growth-factor receptor 3. Prox1: prospero related homeobox 1. Nrp2: neuropilin 2. Tie2: endothelial cell-specific receptor. Ang1 and 2: angiopoietin 1 and 2. SLC: secondary lymphoid chemokine. D6: β-chemokine receptor. ELK3: ETS-domain protein (SRF accessory protein 2). FOXC2: forkhead box C2.

Figure 2

Pulmonary Lymphangiectasia. Chest radiographs, AP views. Radiological findings occurring during the clinical course of PL. A and B: over time progression of hazy perihilar infiltrates on the left lung. C: important bilateral pleural effusion. D: after pleurodesis, bilateral lung hyperinflation with interstitial and septa thickening are evident, and a mild degree of pleural effusion remains.

Figure 3

Pulmonary Lymphangiectasia. High-resolution computed tomography (HRCT). Diffuse thickening of the peribronchovascular interstitium and the interlobular septa (arrowheads), associated with bilateral pleural effusion (*), and peribronchovascular infiltrates (arrows) with bronchogram.

Figure 4

Lymphoscintigraphy. Lymphoscintigraphic study of a patient affected by pulmonary lymphangiectasia and generalized lymphedema showed signs of dermal back-flow in the right lower limb. A and B = patient's hands. L = liver. Arrows point to the thoracic duct.