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Mediastinal and Hilar Lymphadenopathy
Anatomy of the Mediastinum
The mediastinum is the space between the pleural cavities that contains the heart and all chest viscera except the lungs. Consisting of loose areolar tissue and organs, the mediastinum is more a potential space than an actual body cavity. It is bounded laterally by the parietal pleurae, anteriorly by the sternum, posteriorly by the ribs and paravertebral gutters, superiorly by the thoracic inlet, and inferiorly by the diaphragm. The anterior mediastinum contains everything anterior and superior to the heart, including the thymus, aortic arch and its major branches, innominate veins, and lymphatic tissue (nodes and vessels). Most masses here are of thymic origin—teratomas, lymphomas, or angiomatous tumors. The middle mediastinum is triangular with the apex at the fourth thoracic vertebra. It contains the heart, pericardium, trachea, pulmonary hilar and mediastinal lymph nodes and vessels, and phrenic and vagus nerves. Masses in this compartment usually are infectious or are malignant lesions of lymph nodes. The posterior mediastinum extends from the first rib to the diaphragm, behind the heart and lung roots. It contains the esophagus, descending aorta, paravertebral lymph nodes, lower portion of the vagus nerve, and sympathetic nerve chains. Neurogenic tumors and duplication cysts are the most common lesions encountered.
Although the delicacy of mediastinal tissue planes offers little resistance to the spread of disease between compartments, tumors and inflammation tend to extend within compartments. Infections within the mediastinum are relatively uncommon, but their proximity to many vital structures makes accurate diagnosis essential.
Lymphatic Drainage of the Lungs and Pleura
As shown in Fig. 18.1 , lymph from the thoracic viscera (heart, pericardium, lungs, pleura, thymus, and esophagus) traverses one of three possible sets of nodes before entering the thoracic duct or right lymphatic duct. Anterior mediastinal nodes are located anterior to the aortic arch, innominate veins, and large arterial trunks leading from the aorta. They receive afferents from the thymus and pericardium, the sternal nodes, and the thyroid gland.
Posterior mediastinal nodes lie dorsal to the pericardium and adjacent to the esophagus and descending aorta. They receive afferents from the esophagus, dorsal pericardium, diaphragm, and convex surface of the liver. Middle or mediastinal nodes drain the lungs and pleura. Lymphatic drainage of the lungs is composed of superficial and deep plexuses. The superficial plexus lies beneath the visceral pleura. Lymph flows around the border of the lung to enter the bronchopulmonary (hilar) nodes. The deep plexus accompanies branches of the pulmonary vessels and ramifications of the bronchi throughout the lungs.
Lymphatic drainage of the lung passes through four sets of lymph nodes ( Table 18.1 ). Intrapulmonary lymph nodes are located within the lung, chiefly at the bifurcations of the larger bronchi. Bronchopulmonary or hilar nodes are located at the pulmonary hilus at the site of entry of the main bronchi and vessels. Tracheobronchial nodes are divided into superior and inferior groups. The superior group lies in the obtuse angle between the trachea and bronchi on both sides. The inferior, or subcarinal, group lies under the carina at the tracheal bifurcation. The fourth group, the tracheal or paratracheal nodes, lies beside and somewhat anterior to the trachea. A fifth group of lymph nodes of importance in the drainage of the lungs is the inferior deep cervical (scalene or supraclavicular) chain, which is located over the lower portion of the internal jugular vein, just above the clavicle and usually under the scalenus anterior muscle. The apical pleurae drain directly to these deep cervical nodes, as do the paratracheal chains. A finding of supraclavicular lymphadenopathy should lead to investigation for intrathoracic or intra-abdominal pathology.
TABLE 18.1
Lymphatic Drainage of the Lung and Pleura
| Lymph Node Group | Areas Drained |
|---|---|
| Intrapulmonary | Pulmonary vessels, bronchi, and parenchyma |
| Hilar (bronchopulmonary) | Intrapulmonary nodes and superficial plexus of visceral pleural lymphatics |
| Tracheobronchial: superior and inferior (subcarinal) | |
| Right side | All hilar nodes of right lung and hilar nodes of left lower lobe and lingula |
| Left side | Left upper lobe hilar nodes |
| Paratracheal | |
| Right side | Right tracheobronchial nodes |
| Left side | Left tracheobronchial nodes |
| Supraclavicular | |
| Right side | Right apical pleura, right paratracheal nodes, head, neck, arms, and upper thorax |
| Left side (Virchow node) | Left apical pleura, left paratracheal nodes, intra-abdominal nodes, head, neck, arms, and upper thorax |
Ultimately, all lymph from the lungs and pleurae reaches the tracheobronchial and paratracheal lymph nodes. In general, lymph from the lungs flows from left to right, a probable explanation for the preeminence of right upper paratracheal and supraclavicular lymphadenopathy in infectious pulmonary processes, particularly tuberculosis. Lymph from the left lower lobe (and usually also the lingula) flows from the hilar nodes to the lower tracheobronchial nodes, and then to the right paratracheal nodes. Lymph from the right hilar nodes travels to the right paratracheal nodes ( Table 18.1 ).
Lymph vessels from the paratracheal nodes join with lymph trunks from the anterior mediastinum to form the right and left bronchomediastinal trunks. These trunks then join with the lymphatic trunks from the supraclavicular nodes to form the right lymphatic duct and left thoracic duct.
Epidemiology
At least one-third of all mediastinal masses occur in children <15 years; one-half of such masses are symptomatic. Among children with mediastinal masses, 50% who present with symptoms of airway compression have malignant tumors, whereas 90% of those who have noncompressive symptoms have nonmalignant conditions. The greater proportion of symptomatic masses in children compared with adults may be due to smaller thoracic size, resulting in symptoms of compression, or to a higher frequency of malignant lesions. The overall incidence of tumors (excluding metastatic disease) and cysts in the mediastinum is 1 per 100,000 people.
In a series of biopsies of only anterior and middle mediastinal masses in children (thus excluding neurogenic tumors), 1%–57% are reported to be due to histoplasmosis. This extreme variance in rate is due to prevalences of Histoplasma capsulatum in the geographic areas in which studies are done. For example, at St. Jude Children’s Research Hospital in Memphis, histoplasmosis was a relatively common complication in children with cancer, and a reason for referral of children without cancer. Fever with pulmonary infiltrates (frequently nodular) and hilar or mediastinal mass and lymphadenopathy were the usual presentation. Blastomycosis, coccidioidomycosis, and tuberculosis also are associated with infectious mediastinal disease. A variety of other pathogens, including Pneumocystis jirovecii and Mycoplasma spp., can lead to mediastinal lymphadenitis associated with pulmonary infiltrates. Cysts and tumors predominate as the cause of posterior mediastinal lymphadenopathy ( Table 18.2 ). In general, neurogenic tumors are the most common cause of mediastinal masses; lymphomas are second, and germ cell tumors are third in frequency.
TABLE 18.2
Relative Frequencies of Noninfectious Mediastinal Masses in Children a
| Study | ||||
|---|---|---|---|---|
| Silverman and Saleiston | Filler et al. | Woods et al. | Gaebler et al. | |
| Number of children | 437 | 429 | 68 | 37 |
| Frequency of Mass (%) | ||||
| Neurogenic tumor | 40 | 33 | — | — |
| Lymphoma | 18 | 14 | 68 | 43 |
| Leukemia | — | — | 17 | — |
| Germ cell tumor | 11 | 9.8 | — | — |
| Mesenchymal tumor | 7 | 6.8 | — | — |
| Bronchogenic cyst | 7 | 7.5 | — | — |
| Lymph node infection | — | 4.4 | 9 | 57 |
| Other cysts or malignancy | 14 | 25 | 6 | — |
Characteristics of Lymphadenopathy
Lymph nodes are readily identifiable on computed tomography (CT) and can be categorized according to size, shape, coalescence, replacement by tumor mass, presence of calcium, abscess cavities, and parenchymal lung involvement. Most authorities use a 10-mm diameter as the upper limit of normal size for lymph node. , Mediastinal lymph nodes larger than 20 mm virtually are always abnormal; this statement may not be true for hilar nodes. Mediastinal nodes have the potential to become much larger than any other nodes in the body.
Densely calcified bilateral nodes are typical of histoplasmosis and, occasionally, of blastomycosis, coccidioidomycosis, or sarcoidosis. Unilateral densely calcified nodes are typical of prior or late-diagnosed tuberculosis. Benign mediastinal tumors also can be calcified (i.e., teratoma, cystic thymoma, and thyroid adenoma). Childhood lymphomas can cause bilateral hilar adenopathy but usually do not become calcified until after therapy.
In general, mediastinal mass lesions require a tissue diagnosis. Situations in which a biopsy may not be necessary include (1) certain granulomatous lesions that show dense calcification and are not increasing in size, as shown by consecutive imaging studies; (2) lymphomatous lesions diagnosed by biopsy of tissue outside the thorax; and, most important, (3) tuberculosis or histoplasmosis, which should be confirmed with other diagnostic testing.
Clinical Manifestations
Mediastinal lymphadenopathy frequently is asymptomatic until compression or erosion through a mediastinal structure occurs. Table 18.3 delineates findings associated with mediastinal disease. Respiratory symptoms result from airway obstruction or erosion. If the obstruction is significant enough, distal obstructive emphysema, atelectasis, pneumonia, or chronic, recurrent respiratory tract infections can result. Obstruction of the superior vena cava is a rare complication that is most commonly associated with rapidly growing malignant mediastinal tumors. The superior vena cava is particularly vulnerable to obstruction because of its thin wall, low intravascular pressure, and confinement by lymph nodes and other rigid structures. Older children with mediastinal masses may describe feeling intrathoracic discomfort or pain, which probably is due to pressure on intercostal nerves or pleura. Vertebral erosion secondary to posterior mediastinal tumors can cause a boring, interscapular pain. Most children with mediastinal disease caused by histoplasmosis present with chest pain or cough.
TABLE 18.3
Symptoms of Compression Resulting From Mediastinal Adenopathy
| Structure | Symptom or Sign |
|---|---|
| Airway | Cough, wheezing; recurrent respiratory infections, bronchitis, atelectasis, unresolved pneumonia; hemoptysis; chest pain, sudden death |
| Esophagus | Dysphagia (interruption of peristalsis); hematemesis (fistula formation) |
| Superior vena cava | Dilation of collateral veins of the neck and upper thorax; chemosis of conjunctiva; edema of face, neck, upper chest, and arm; cyanosis; headaches, visual disturbances; epistaxis, tinnitus |
| Lymphatic channels | Pleural effusion |
| Recurrent laryngeal nerve | Hoarseness, inspiratory stridor (paralysis of vocal cord) |
| Phrenic nerve | Paralysis of left diaphragm |
| Sympathetic ganglia | Horner syndrome |
| Vertebrae, ribs | Pain secondary to bony erosion; symptoms of spinal cord compression |
The finding of mediastinal widening, regardless of symptoms, leads to evaluation by CT. The diagnosis of lymphoma is considered first. If granulomatous lung disease is present, the diagnosis of tuberculosis is considered, as is histoplasmosis in endemic regions. History of travel, foreign birth, consumption of unpasteurized milk, or farm or bird exposure is sought.
Diagnosis
Historically, the differential diagnosis of mediastinal masses evident on chest radiograph was considered according to location within one of the four mediastinal compartments. Use of CT has largely supplanted the need for this classification because distinct tissue groups are now defined: fat, lymph nodes, vessels, airways, thymus, esophagus, and paraspinal tissues.
Imaging Studies
CT is the imaging study of choice for children with mediastinal mass. Unenhanced CT augments recognition of calcification. CT with administration of contrast material is useful to better define anatomy and distinguish vessels from lymph nodes. Identification of a solid, homogeneously enhancing soft tissue mass can distinguish lymphoma from cavitating lesions of histoplasmosis and tuberculosis, which are peripherally enhancing with low attenuation centrally. With the widespread use of multidetector helical CT, multiplanar imaging now is routine and allows definition of mediastinal structures in all planes. Magnetic resonance imaging (MRI) is required infrequently to evaluate the mediastinum because most lesions are visualized well on multidetector helical CT. In addition, MRI often requires sedation (which can be dangerous in the presence of intrathoracic mass) and cooperation of the child to hold their breath (lest there be motion artifact). MRI is used for specific problem solving, such as evaluation of soft tissue masses of the chest wall, and when neurogenic lesions are suspected, to evaluate extension into the spinal canal.
Although CT and MRI are highly sensitive for detecting enlarged lymph nodes, neither reliably distinguishes between benign and malignant causes. Both can show displacement or compression of trachea or esophagus, but neither distinguishes invasion. MRI has the limitation of being less able to demonstrate calcifications and is highly sensitive to motion (breathing or heart contraction) artifact.
Tissue Diagnosis and Biopsy
In general, mediastinal mass lesions require a tissue diagnosis because of likely causes and their proximity to vital structures. In some cases, a diagnosis can be made without obtaining mediastinal tissue. Laboratory examination of supraclavicular nodes (whether enlarged or not) or other enlarged extrathoracic nodes can be diagnostic. In one-half of children with mediastinal malignancy, at least one lymph node in the cervical, supraclavicular, or infraclavicular or axillary area is larger than 2 cm and can be biopsied. Tissue biopsy from other sites, along with serologic testing, can confirm sarcoidosis. Bronchoscopy with bronchoalveolar lavage or gastric aspirates may identify an infectious cause.
Infectious Causes
Table 18.4 shows differentiating features of the causes of mediastinal lymphadenopathy. Mycobacteria and the endemic fungi, Histoplasma and Coccidioides, commonly cause hilar and mediastinal adenopathy. Although mediastinal infection without significant pulmonary infection is rare, the degree of adenopathy frequently is disproportionate to degree of parenchymal involvement. Pneumonia due to Mycoplasma pneumoniae, Bartonella henselae, Yersinia enterocolitica, or Francisella tularensis can be associated with hilar adenopathy, as can bronchiectasis and cystic fibrosis. Adenopathy is rare in other acute bacterial and viral pneumonias.
TABLE 18.4
Causes of Mediastinal Lymphadenopathy
| Etiology | Frequency | Associated Pneumonia | Node Abscess | Node Calcification | Method of Diagnosis |
|---|---|---|---|---|---|
| Infectious Causes | |||||
| Bacteria | |||||
| Mycobacterium tuberculosis | ++ | ++ | ++ | ++ | Tuberculin skin test/IGRA; chest radiograph; culture and nucleic acid amplification of gastric aspirate or bronchial washing |
| Nontuberculous mycobacteria | + | − | + | − | Culture and histopathologic analysis of tissue |
| Mycoplasma pneumoniae | + | ++ | − | − | Serology |
| Bartonella henselae | + | − | + | − | Serology; culture; histopathology |
| Yersinia enterocolitica | + | − | + | − | Culture; serology |
| Actinomyces species | + | − | + | − | Culture; histopathology |
| Melioidosis | ± | − | + | − | Culture |
| Fungi | |||||
| Histoplasma spp. | ++ | + | + | ++ | Serology; antigen detection; culture |
| Coccidioides spp. | + | + | + | + | Serology; culture |
| Blastomyces spp. | + | ++ | + | + | Culture |
| Paracoccidioides spp. | + | + | ++ | Culture | |
| Cryptococcus spp. | + | + | − | − | Culture |
| Viruses | |||||
| Epstein-Barr virus | + | − | − | − | Serology |
| Protozoa | |||||
| Toxoplasma spp. | ± | − | − | − | Serology |
| Chronic Infection | |||||
| Cystic fibrosis | ++ | ++ | + | − | Sweat test; gene identification |
| Bronchiectasis | + | + | + | − | Radiograph; culture |
| Lung abscess | ± | + | − | − | Radiograph |
| Noninfectious Causes | |||||
| Malignancy | |||||
| Hodgkin lymphoma | ++ | ± | − | + a | Biopsy |
| Non-Hodgkin lymphoma | ++ | − | − | + a | Biopsy |
| Leukemia | + | − | − | Bone marrow | |
| Other | |||||
| Chronic granulomatous disease | + | + | ++ | − | Neutrophil function assay |
| Sarcoidosis | ++ | − | − | − | Biopsy |
| Rosai-Dorfman disease | + | − | − | − | Biopsy; histopathology |
| Castleman disease | + | − | − | − | Biopsy; histopathology |
| Lymphoproliferative syndromes | ++ | − | − | − | Epstein-Barr virus serology; biopsy |
| Graves disease | ± | − | − | − | Thyroid hormone measurement |
++, frequent; +, occasional; ±, rare, consider under special circumstances; IGRA, interferon-γ release assay.
Bacterial Causes
Mycobacterium tuberculosis
Primary pulmonary infection with M. tuberculosis has the following three elements: the primary parenchymal focus, intraparenchymal lymphangitis, and regional lymphadenitis ( Figs. 18.2 and 18.3 ). At least 70% of primary pulmonary foci are subpleural, with spread through lymphatics to the regional lymph nodes. After several weeks, hypersensitivity develops, with regional node enlargement and the potential for caseating necrosis. Caseating lesions have a high density of actively multiplying bacilli, which spread rapidly to adjacent lymphatics. The hallmark of early tuberculosis is excessive unilateral mediastinal lymphadenitis compared with the relatively insignificant focus in the lung. Hilar adenopathy is unilateral in 80% or more of cases of tuberculosis.
Infection can spread beyond the hilar and tracheobronchial nodes to the more distant right upper paratracheal nodes (the ones most often affected) and deep cervical (supraclavicular) nodes. In addition, apical subpleural primary infections can drain directly to the supraclavicular nodes. In one series of patients, 14 of 54 patients with a primary lesion in the right upper lobe had ipsilateral enlargement of deep cervical nodes.
Enlargement of hilar nodes adjacent to bronchi can cause bronchial obstruction with the collapse or consolidation or fan-shaped segmental lesion typical of childhood tuberculosis. Infection and inflammation of the bronchial wall can occur, and obstruction of the lumen rarely can result in sudden death or in obstructive hyperaeration, segmental atelectasis, or secondary pneumonia. Multiple segmental lesions can occur, usually in the same lung.
Calcification follows caseous necrosis and occurs more often in children and in the regional lymph nodes than in the primary pulmonary focus. Extensive calcification is uncommon with early treatment, which prevents caseation.
In one series of CT imaging performed in 23 young adults presenting with tuberculous mediastinal or hilar lymphadenitis, pulmonary involvement was demonstrated in 14 patients. There was remarkable preponderance of involvement of the right paratracheal and tracheobronchial nodes. Nodes >20 mm in diameter invariably showed central areas of relatively low density and peripheral rim enhancement that was irregular in thickness.
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