Nonmalignant Adult Thoracic Lymphatic Disorders Maxim Itkin, MD, FSIRa,*, Francis X. McCormack, MDb KEYWORDS Lymphangioma Lymphangiomatosis Lymphangiectasia Generalize lymphatic anomaly (GLA) Gorham-Stout disease (GSD) Kaposiform lymphangiomatosis (KL) Pulmonary lymphangiectasia Yellow nail syndrome KEY POINTS The thoracic lymphatic disorders typically present with symptoms of cough, shortness of breath, chyloptysis, or expectoration of branching casts. Typical pulmonary manifestations of the thoracic lymphatic disorders include chylous effusions, peribronchiolar interstitial infiltrates, and mediastinal masses. The emergence of sophisticated imaging techniques that characterize abnormal lymphatic flow promises to improve the classification and therapeutic approaches to the thoracic lymphatic disorders. INTRODUCTION conduits coursing on the surface of major airways in the hila and mediastinum and ultimately drain Primary lymphatic anomalies comprise a bewil- into the right lymphatic duct and thoracic duct dering array of congenital and acquired conditions (TD). The right lymphatic duct inserts into the sub- that can affect every organ system containing clavian vein in the neck and drains the right upper lymphatic channels, generally considered to be lobe. The TD inserts into the left innominate vein at all tissues except brain and bone marrow. the junction with the internal jugular vein and Lymphatic anomalies usually come to medical drains the left lung, right middle and lower lobes attention during childhood or early adulthood, of the right lung, as well as all structures below but can also present later in life. For the purpose the diaphragm (Fig. 1). A broad discussion of of this article, the discussion focuses on the lymphatic anatomy is beyond the scope of this lymphatic disorders that involve thoracic struc- article, but it is important to note that intestinal tures, either primarily or as part of a more global lymph (chyle) that contains chylomicrons (dietary lymphatic disease process, and which preferen- fats) enters the TD at the level of cisterna chyli in tially affect older children and adults. the upper abdomen and is transported to the The pulmonary lymphatics are a network of ves- venous system in the neck. The primary route thor- sels that function to transport cells and fluids from ough which chylous fluid reaches the pleural space the periphery of the lung to the central lymphatic or other thoracic structures in subjects with conduits, in order to regulate tissue pressure and chylous effusions, therefore, is either through (1) facilitate regional immune responses. The periph- reflux from an obstructed or pressure-overloaded eral lymphatic vessels converge on the larger Disclosures: None. a Interventional Radiology, Hospital of the University of Pennsylvania, Penn Medicine, 1 Silverstein, 3400 Spruce Street, Philadelphia, PA 19104, USA; b Division of Pulmonary, Critical Care and Sleep Medicine, Univer- sity of Cincinnati, MSB 6165, 231 Albert Sabin Way, Cincinnati, OH 45267-0564, USA * Corresponding author. E-mail address: [email protected] Clin Chest Med 37 (2016) 409–420 http://dx.doi.org/10.1016/j.ccm.2016.04.004 0272-5231/16/$ – see front matter Ó 2016 Elsevier Inc. All rights reserved. chestmed.theclinics.com 410 Itkin & McCormack Visceral pleura Contralateral Ipsilateral Visceral lymphatics course course pleura lymphatics Peribronchovascular lymphatic collectors Peribroncho- vascular lymphatic collectors Ipsilateral course Inferior Contralateral pulmonary course ligament Inferior pulmonary ligament Intra-abdominal Intra- collector abdominal collectors Visceral Visceral pleura pleura lymphatics lymphatics Arch of thoracic duct Right lymphatic Arch of collector arches thoracic duct Superior Left vena cava paratracheal collectors Right tracheobronchial node Right paratracheal Aortopulmonary collectors node Left tracheobronchial node Subcarinal node Fig. 1. Schematic representation of pulmonary lymphatic anatomy. (Adapted from Riquet M. Bronchial arteries and lymphatics of the lung. Thorac Surg Clin 2007;17:619–38; with permission.) TD into the pulmonary lymphatic stream, or (2) Extrapulmonary manifestations of the TLDs can through a pathologic connection between chylous include lymphatic leaks in various distributions lymphatics and the pleural space, airways, or lung (eg, chylous ascites), protein-losing enteropathy, parenchyma, as can occur following surgery or recurrent fevers and prostration, lymphatic trauma or as part of a pathologic process. Other obstruction resulting in lymphedema of extrem- thoracic chylous complications that can result ities, coagulopathy, and bony lesions. The TLDs from these 2 processes include chylous conges- often present in protean manner and can be tion in the lung parenchyma,1 plastic bronchitis congenital or acquired, localized or systemic. (PB; expectoration of branching casts),2 chyloper- Attempts to classify these disorders have gener- icardium, and chyloptysis. ally been based on defining commonalities of a The thoracic lymphatic disorders (TLD) limited number of cases or the consensus of comprise a group of diseases that are variably experts.3–6 Most of the published classification associated with mediastinal or pulmonary masses, systems use inconsistent terminology and lack interstitial infiltrates, airway disorders including clear diagnostic, clinical, laboratory, or imaging chyloptysis, PB, pleural effusions that are often standards. The TLDs are often grouped based on chylous, and repeated pulmonary infections and symptoms, age of presentation, histologic appear- bronchiectasis (eg, yellow nail syndrome, YNS). ance, associated illnesses, or secondary imaging Nonmalignant Adult Thoracic Lymphatic Disorders 411 findings rather than on unifying pathologic including lymphangioleiomyomatosis (LAM), or processes. YNS. The disorders we have chosen to discuss Common terms that have been used to describe below are a subset of TLDs that might conceivably primary lymphatic disorders include lymphan- present with pulmonary infiltrates, thoracic gioma, lymphangiectasia, lymphangiomatosis, masses, or chylous leaks in an adult pulmonary primary lymphedema,7 pulmonary lymphangiecta- clinic, including lymphangioma (a term that has sia (PL),8–10 intrathoracic lymphangiomatosis,11 now been replaced with microcystic or macrocys- thoracic lymphangiomatosis,12 diffuse pulmonary tic lymphatic malformation), diffuse pulmonary lymphangiomatosis,13 and mediastinal lymphan- lymphangiomatosis (DPL; a term that is obsolete giomatosis.14 The mode of clinical presentation is but without an accepted replacement, here called often added to modify these disease classifica- primary pulmonary lymphatic anomaly [PPLA]), tions, using terms idiopathic, congenital, neonatal, GLA with pulmonary involvement, a new subtype or acquired to describe chylothorax, chylous asci- of GLA called Kaposiform lymphangiomatosis tes, or chylopericardium.15–18 (KLA), lymphatic malformation in GSD, PB, and In particular, the terms lymphangioma and lym- YNS. Disorders that are exclusively found in neo- phangiectasia have been used interchangeably to nates primarily, are malignant, or which do not describe a heterogeneous group of disorders typically involve thorax, such as congenital chylo- associated with excess lymphatic tissue. Although thorax, primary lymphedema, Kaposi sarcoma, or both conditions are very similar histologically,6,19 lymphangiosarcoma, are not discussed in this by definition lymphangiomas are sequestered article. An overriding theme in this review is the from the main lymphatic system, and lymphan- importance of lymphatic imaging in classifying giectasias are connected to it. The primary means and treating these disorders. to differentiate between these 2 disorders clinically is with imaging capable of revealing lymphatic THORACIC LYMPHANGIOMAS (MICROCYSTIC flow. Revealing lymphatic flow was formerly AND MACROCYSTIC LYMPHATIC accomplished with pedal lymphangiogram and MALFORMATIONS) lymphoscintigraphy,20,21 which have been re- ported to demonstrate pathologic lymphatic flow Lymphangiomas are focal proliferations of well- (“lymphatic reflux”) in lymphangiectasia despite differentiated lymphatic tissue that present as its limitations in anatomic definition.22–24 Over the multicystic or sponge-like accumulations.19,28 In last few decades, however, these procedures many cases, they represent embryologic rem- have been less frequently performed and the nants of lymphatic tissues. Acquired or second- expertise required to execute them has been lost ary lymphangiomas can occur at the site of to many radiology departments. Intranodal radiation, trauma, or infection. Cystic lymphan- lymphangiogram (IL)25 and dynamic contrast- giomas (also known as cystic hygromas or cystic enhanced magnetic resonance lymphangiogram hydromas) can occur anywhere but are most (DCMRL)26,27 are new imaging techniques common in the armpit and the neck. In the that can better define lymphatic anatomy and thorax,theymanifestasmassesinthemedias- lymphatic flow. These approaches have tinum,29,30 pleura,31,32 or intrapulmonary33 distri- opened new vistas in the understanding the impor- butions (Fig. 2). Mediastinal lymphangiomas are tance of lymphatic flow in primary lymphatic equally distributed between the anterior, poste- disorders26,27 and will likely lead to more rational rior, and medial mediastinal compartments and approaches to classification. often envelop and displace mediastinal vessels. The International