Diseases of the thoracic lymphatic system have a variety of radiographic manifestations reflecting their pathophysiology and pathologic anatomy. We will review the radiology of lymphangiomas, lymphangiohemangiomas, pul monary lymphangiomatosis, lymphangiectasis, lymphangioleiomyomatosis, lymphatic dysplasia, and traumatic lymphatic injury. In addition, diseases with a lymphatic distribution will also be discussed, including lymphangitic carcinomatosis, sarcoidosis, pulmonary lymphoma, and Kaposi sarcoma (KS).

The thoracic lymphatic system contains two distinct lymphatic drainage portals. The first is superficial, draining the lung surface and the subpleural portion of the lung. The second drains the remainder of the lung parenchyma via channels along bronchi and vessels and in interlobular septa. Both of these systems converge at the pulmonary hilum before draining into either the thoracic duct or brachiocephalic veins [1].

The anatomy of the secondary pulmonary lobule helps in understanding manifestations of lymphatic disease. The lobule is the smallest unit of lung marginated by connective tissue and is usually polygonal, about 1–2 cm on a side. The margins are the interlobular septa, containing pulmonary veins and lymphatics. Thus, lymphatic abnormalities can result in interlobular septal thickening. Lymphatics do not extend into the alveolar walls, meaning that fine intralobular interstitial thickening, typically a sign of pulmonary fibrosis, is not a feature of lymphatic disorders.

The embryology of the lymphatic system is poorly understood. According to the angioblast theory, pulmonary lymphatics develop at the hilum as buds from the pulmonary veins and then ramify out into the parenchyma until their connections with the veins are lost. Under this theory, developmental anomalies such as lymphangiectasis might result from uncontrolled proliferation at the initial stage. According to the local origin theory, lymphatics develop not from veins but from outside in as peripheral endothelium-lined spaces coalesce into lymphatic channels. This theory explains how the abnormal lymphatic channels in lymphangiomatosis and lymphangiectasis are isolated from the normal parts of the lymphatic system [2]. Ultimately, neither theory adequately explains all the features of pulmonary lymphatic diseases.

A congenital, benign lesion that results from focal, excessive proliferation of lymphatics, lymphangioma can occur in many organs [3, 4]. It represents an isolated cluster of abnormal lymphatics that swells as lymph accumulates within it [4]. The most common location is the neck (where lymphangioma is referred to as “cystic hygroma”); in the thorax, it is usually mediastinal, constituting about 4.5% of all mediastinal masses [4, 5]. Rarely, lymphangioma presents as a solitary intrapulmonary lesion [3]. Other rare locations are the pulmonary hila and the pericardium [6]. Overall, lymphangioma is more common in women than men, with a mean age at diagnosis of 36.5 years [5]. For the most part, lymphangioma is asymptomatic unless it grows enough to press on adjacent structures [7].

The imaging findings of lymphangioma are similar to those of other cystic mediastinal masses (Figs. 1 and 2A, 2B, 2C). Although typically homogeneous, thin-walled, well-circumscribed, and low in attenuation, a lymphangioma may contain higher-attenuation fluid reflecting high protein content, hemorrhage, or infection. Calcification or contrast enhancement is atypical and suggests a different diagnosis. Classically, as in the neck, these lesions insinuate and spread throughout the mediastinum. Unlike in the neck, where septation may be visible on CT, in the chest, visible septation is unusual [5]. On MRI, the cyst shows high T2 and low T1 signal. Internal septations are more apparent than on CT, especially on gadolinium-enhanced or T2-weighted images [8] (Fig. 3A, 3B, 3C, 3D). The most common locations are the anterior and superior and right paratracheal parts of the mediastinum [8]. The pathologic subtypes of lymphangioma (simple, cystic, and cavernous) cannot be distinguished by CT or MRI [9].

Imaging of lymphangioma defines the extent of disease and aids surgical planning, but there are no imaging features that permit specific diagnosis. The lesion is usually resected, given the possibility of infection and the potential for symptoms as the lesion grows. However, the insinuating and infiltrating nature of the lesion makes complete resection of lymphangioma difficult, and local recurrence is common [9].

Lymphangioma rarely occurs within the lung, where it is typically well circumscribed but occasionally spiculated and irregular [3, 4]. It cannot reliably be distinguished from a tumor.

This rare lesion clinically behaves like lymphangioma and is often misdiagnosed as a lymphatic malformation. Lymphangiohemangioma is a low-flow lesion combining vascular and lymphatic elements, which alter the imaging findings [10]. Depending on the extent of the vascular component, there can be homogeneous or heterogeneous contrast enhancement. Tiny cysts correspond to dilated lymphatic channels. Local infiltration can result in incorporation of mediastinal fat, creating the appearance of fatty tumor [11]. Phleboliths, punctate calcifications, and puddling contrast enhancement, which are characteristic of pure hemangioma, have not been reported but are possible given the vascular elements (Fig. 4A, 4B, 4C). The anterior mediastinum is probably the most common location, but there are too few reported cases to be certain [12].

Lymphangiomatosis is a rare, systemic, multiorgan disease resulting in marked proliferation and dilation of lymphatics [13]. It is most common in children and affects both sexes equally [13]. It can involve any part of the body containing lymphatics but tends to involve the chest and mediastinum [13]. Lymphangiomatosis is probably congenital, but it presents later, presumably because of hormonal stimulation [13]. It differs from pulmonary lymphangiectasis in that the lymphatics are not only dilated, but also increased in number and extensively interconnected [6, 14]. Lymphangiomatosis is histologically benign, but it infiltrates widely. It is more aggressive in patients who present at a younger age [14], usually with progressive dyspnea leading to death from respiratory failure [15]. Mortality is high because it cannot be cured by resection, radiation, or chemotherapy [9, 16].

Proliferation of lymphatic channels [14] explains the imaging findings (Figs. 5A, 5B, 5C, 5D, 5E, 5F, 5G, 5H and 6A, 6B): diffuse, bilateral, symmetric, and interlobular septal and peribronchovascular thickening [14, 17]. The interlobular septal thickening is typically smooth but sometimes nodular [17]. Findings may have upper lobe predominance [17]. Patchy ground-glass attenuation can reflect edema, hemorrhage, or the accumulation of hemosiderin-laden macrophages [6, 14]. The disease affects lymphatics and usually spares alveolar spaces [16].

Lymphatic proliferation diffusely infiltrates the mediastinum and thickens the visceral and parietal pleura. Despite extensive infiltration, mass effect on mediastinal structures is unusual [17], and there is surprisingly little lymphadenopathy [14]. Finally, pleural effusion is common, either serous or chylous [17]. Extrathoracic findings include lytic bone lesions, spleno megaly, splenic lesions, and disseminated intravascular coagulation or other coagulopathy [6].

Pulmonary lymphangiectasis is a congenital abnormality that causes dilation of septal, subpleural, and peribronchial pulmonary lymphatics and carries high mortality; nearly 50% of infants are stillborn [2, 18] and others usually die of respiratory distress within hours of birth [2]. Similar in histopathology to pulmonary lymphangiomatosis, pulmonary lymphangiectasis presents at a younger age (usually shortly after birth) and has a much more rapidly progressive course. It is probably more common in males, and it is associated with Down and Noonan syndromes and with cardiac anomalies, such as total anomalous pulmonary venous return, hypo plastic left heart, atrioventricular valve defect, and pulmonic stenosis [2, 4, 18, 19].

Most cases are classified as primary lymphangiectasis, likely resulting from failure of interstitial connective tissue to regress during the fifth month of development [13]. However, a few cases affect only one or two lobes of a single lung and can thus be treated by resection [20]. When the condition causes lymphatic dilation in organs outside the thorax, the lung abnormalities tend to be milder and life expectancy better [2]. Rarely, there can be secondary lymphangiectasis resulting from lymphatic or venous outflow obstruction from congenital heart disease, congenital thoracic duct hypoplasia, or radiation [1, 13].

On pathologic examination, the lungs are bulky and noncompliant, with markedly dilated lymphatics in interlobular septa and subpleural and peribronchovascular spaces. Peripheral lung cysts are present, likely representing dilated lymphatic channels [18].

CT findings resemble those of pulmonary lymphangiomatosis (Fig. 7): bilateral groundglass opacity, smooth interlobular septal thickening, marked pleural thickening, and mediastinal soft-tissue infiltration [21]. The lung findings may be concentrated in perihilar and subpleural regions [1]. Up to 15% of patients may have pleural effusions, which are often chylous [1]. Conclusive diagnosis requires lung biopsy, although clinical features and age at presentation may help distinguish lymphangiectasia from lymphangiomatosis.

In lymphangioleiomyomatosis (LAM), the fundamental disorder is abnormal smooth-muscle proliferation in the lung, but the involvement of lymphatics justifies including it with other lymphatic disorders. It is rare (2.6 cases per million) and primarily affects women of child-bearing age. LAM leads to respiratory failure, often requiring lung transplantation. It can also cause recurrent pneumothorax and chylous pleural effusion [2, 22]. There is a strong association between LAM and the tuberous sclerosis complex, with up to one third of women with tuberous sclerosis complex presenting with LAM [22].

The pathophysiology of LAM is abnormal proliferation of smooth muscle cells (LAM cells), which can obstruct bronchi, veins, and lymphatics. Obstruction of bronchioles leads to the classic radiographic finding: multiple, round, thin-walled, regular lung cysts that can involve any part of the lung (unlike Langerhans cell histiocytosis, in which cysts spare the costophrenic angles) [2, 23]. The cysts tend to be regular and round, but can lose roundness when confluent [24]. Lung involvement is typically symmetric and uniform, without air trapping [24] (Figs. 8A, 8B, 8C, 8D, 8E and 9A, 9B, 9C, 9D). Pneumothorax is the presentation in 40% of cases, and recurrent pneumothorax may necessitate pleurodesis [24].

When smooth-muscle proliferation obstructs lymphatics, it can cause recurrent chylous pleural effusion. The effusion can be unilateral or bilateral and can be large enough to cause dyspnea. Chylous and serous effusions cannot be distinguished by CT. Treatment is difficult and repeated thoracentesis can cause protein loss [24].

Smooth-muscle proliferation can also lead to obstruction of mediastinal and retroperitoneal lymphatic channels and formation of lymphangioleiomyomas. These cystic lymphatic channels have thin or thick walls and contain low-attenuation fluid. They are less common in the mediastinum than in the abdomen, where they are found in up to 20% of cases (Fig. 9A, 9B, 9C, 9D). Finally, dilation of the thoracic duct is common in LAM [24].

The term “lymphatic dysplasia” encompasses a number of disorders that have been classified in different ways [25]. Included are primary lymphedema syndrome, congenital chylothorax, idiopathic chylous effusion, and the yellow nail syndrome (lymphedema, effusion, and nail dysplasia) [13]. These syndromes are characterized by either hypoplasia or aplasia of the proximal or peripheral lymphatics and, in some cases, incompetent lymphatic valves [13].

These rare conditions (0.1 per 100,000) present in childhood or young adulthood, more commonly in women, with lymphedema of an extremity, chylothorax, or chylous pericardial effusion [13]. There are associations with Noonan and Turner syndromes [26].

Injury to the thoracic duct can lead to chylothorax [36], which is reported in about 2% of some trauma series [37]. Injury is more often caused by penetrating than blunt trauma and usually only from hyperextension spine injuries or posterior rib fracture [36, 38]. Only 0.06% of thoracic duct lacerations are isolated injuries [38]. Thoracic duct injury can be an iatrogenic complication of percutaneous and open surgical procedures, particularly esophagectomy [37].

Although often overshadowed by concomitant injuries, thoracic duct injury with chylothorax causes morbidity and mortality. Low-volume leaks are usually treated conservatively with drainage of the effusion and dietary restriction to minimize the production of chyle. Management of the leak is often difficult [38], and persistent drainage after 2 weeks typically leads to ligation of the thoracic duct [36].

CT cannot directly show the injury to the thoracic duct [39] and serves only to document the persistent pleural effusion (Fig. 16). In addition, the course of the thoracic duct is variable, limiting the usefulness of CT. Only 65% of people have usual ductal anatomy, and up to 33% have two thoracic ducts [38]. Also, CT does not distinguish chylous from serous pleural effusion (Figs. 16 and 17). Of more use is lymphangiography, which may show the site of the leak [37].

Both contrast-enhanced and unenhanced MRI techniques have been developed for the lymphatic system, such as gadolinium-based T1-shortening agents that can be injected intradermally or subcutaneously and taken up into the lymphatic system [40, 41]. Contrast agents can be taken up into the reticuloendothelial system after IV administration. CT lymphangiography is another avenue for future exploration [40].

The radiographic findings of primary lymphatic disorders and diseases with a lymphatic pattern of spread can be explained by the anatomy of lymphatics in the chest. Lymphatic disorders should be kept in mind when CT shows smooth or nodular septal thickening, perilymphatic nodules, and a peribronchovascular distribution of disease. In addition, lymphangioma and lymphangiohemangioma should be considered when CT shows a cystic mediastinal or retroperitoneal mass.

Address correspondence to S. N. J. Pipavath ([email protected]).