Bilateral hilar lymphadenopathy

Bilateral hilar lymphadenopathy is a bilateral enlargement of the lymph nodes of pulmonary hila ¹. Bilateral hilar lymphadenopathy is a radiographic term for the enlargement of mediastinal lymph nodes and is most commonly identified by a chest x-ray.

For the diagnosis of pathologically enlarged nodes, information about normal node size is required. Commonly used metrics for lymph node measurement include the maximum and minimum axial diameters, and the ratio of these two values ². The shortest axial diameter appears to be a more useful parameter than the greatest axial diameter, although a different threshold should be used for each nodal station ³.

The generally accepted size criterion for mediastinal lymph node enlargement (>10 mm along the short axis) has been applied to all patients when staging lymphoma or bronchogenic carcinoma ⁴. Other authors use the following standard maximum normal short-axial diameters for nodal regions: region 7, 12 mm; regions 4 and 10R, 10 mm; and other regions, 8 mm. Maximum greatest axial diameters show wider variation, ranging from 10 to 25 mm ⁵.

Bilateral hilar lymphadenopathy causes

Bilateral hilar lymphadenopathy or bilateral hilar lymph node enlargement can arise from many causes, which include ¹:

• Sarcoidosis: Sarcoidosis is a systemic granulomatous disease that affects primarily the lung and lymphatic system. Five radiological stages of intrathoracic changes have been defined: stage 0, no visible intrathoracic finding; stage 1, lymphadenopathy only; stage 2, lymphadenopathy with parenchymal infiltration; stage 3, parenchymal disease only; and stage 4, pulmonary fibrosis ⁶. Lymphadenopathy is seen in stages 1 and 2. The most common pattern is bilateral hilar and right paratracheal lymphadenopathy, also known as Garland’s triad. The left paratracheal nodes and the aortopulmonary window nodes are also commonly enlarged ⁷. In general, when multiple lymph node groups in the hila and mediastinum are symmetrically enlarged in a young patient, sarcoidosis is the most likely diagnosis. Amorphous, punctate, or eggshell-like calcifications may also be seen and are suggestive of a chronic condition, occurring in 3% of patients after 5 years and in 20% after 10 years ⁸.
• Infection
  • Tuberculosis
  • Nycoplasma
  • Histoplasmosis
  • Pulmonary coccidioidomycosis
• Malignancy
  • Lymphoma: more common in Hodgkin lymphoma than non-Hodgkin lymphoma.
  • Carcinoma
• Inorganic dust disease
  • Silicosis: Silicosis is caused by the inhalation of free silica particles during occupational exposure –such as in mining, drilling, and sandblasting –which leads to a fibrous tissue reaction in the lungs ⁹. The classical features of patients with silicosis are diffuse interstitial shadowing with bilateral enlargement of hilar lymph nodes, which may or may not be calcified ¹⁰. Antao et al. ¹¹ also found that 74% of silicotic patients had enlarged mediastinal lymph nodes and 66% of exposed workers had evidence of lymph node calcification. Eggshell calcification is the most common pattern described in silicosis ¹², although some authors have reported that the puncate pattern is most prevalent ¹¹.
  • Berylliosis: Berylliosis is a lung disease caused by the inhalation of beryllium (Be) compounds. Berylliosis can lead to acute chemical pneumonitis – due to intense exposure to beryllium within a short time – or chronic interstitial lung disease, after prolonged exposure to lower beryllium concentrations. The chronic form is more common and presents as intraalveolar accumulation of lymphocytes and macrophages, alveolitis, and noncaseating granulomas ¹³. CT appearances of chronic berylliosis are similar to those of sarcoidosis, although mediastinal and hilar lymphadenopathy are less common, occurring in about 25% of patients. Berylliosis should be included in the differential diagnosis for all patients with imaging appearances suggestive of sarcoidosis ¹⁴.
• Heart failure: Chronic left heart failure may cause mediastinal lymphadenopathy. Several mediastinal lymphatic chains are involved, but the subcarinal, paratracheal, and hilar nodes are more frequently affected. The mechanisms underlying the pathogenesis of lymphadenopathy in cardiogenic pulmonary edema are not completely clear, but it has been suggested to be the expression of diffuse intrathoracic edema affecting the pulmonary parenchyma and neighboring structures, including the mediastinum and associated lymph nodes ¹⁵. Lymphadenopathy has been suspected based on features observed on radiographs taken to investigate dyspnea and heart failure. The identification of suspicious features is theoretically easier on follow-up radiographic examinations, which provide better visibility of hilar and mediastinal areas, after treatment to reduce pulmonary edema ¹⁵.
• Cryptogenic organizing pneumonia or bronchiolitis obliterans-organizing pneumonia ¹⁶
• Amyloidosis: Amyloidosis is characterized by the accumulation of inappropriately folded protein deposits. Amyloidosis may be localized, but it is much more commonly diffuse, affecting organ function by replacing the normal cell structure. Based on the structure of the fibrillar protein –one of the deposit’s components–amyloidosis is classified into several types, most commonly primary and secondary ¹⁷. Hilar and mediastinal lymph node enlargement is not described in secondary amyloidosis, and is uncommon in localized amyloidosis. However, it is quite common in primary amyloidosis. Thoracic lymphadenopathy, alone or with interstitial disease, is the most common CT finding in primary amyloidosis. Mediastinal and hilar lymph nodes may be involved, bilaterally and often massively, resulting in a pattern that may resemble sarcoidosis. Calcification is usually described as coarse or nonspecific, and eggshell calcification may be seen. Associations with nephrotic syndrome, congestive heart failure, and neuropathy can help identify the disease ¹⁸.
• Castleman’s disease: Castleman’s disease is an uncommon, mainly benign, lymphoproliferative disorder of unknown cause. The overall prevalence of the disease is estimated to be less than 1/100,000 ¹⁹. Castleman’s disease may be localized or multifocal. The former presents few or no symptoms, so its diagnosis is made typically through incidental radiological findings. On chest radiographs, it may appear as an incidental, rounded, solitary mediastinal or hilar mass with a differential diagnosis that includes thymoma, lymphoma, neurogenic tumor, and bronchial adenoma ²⁰. On CT, it usually manifests as a homogeneous, noninvasive, large, solitary mass with soft-tissue attenuation, most commonly in the mediastinum or hila ²¹.
• Idiopathic pulmonary fibrosis: Idiopathic pulmonary fibrosis is a specific form of chronic fibrosing interstitial pneumonia limited to the lung ²². The reported prevalence of mediastinal lymphadenopathy in idiopathic pulmonary fibrosis is 66% (90/136 patients) ²³ or, similarly, 70% ²⁴. The presence of enlarged mediastinal nodes may indicate a more chronic and advanced disease process ²⁵. Jung et al. ²⁶ showed that the total number of enlarged lymph nodes increased with the severity score of pulmonary fibrosis. Idiopathic pulmonary fibrosis was reported to be associated with an increased risk of lung cancer, due to the occurrence of atypical or dysplastic epithelial changes in fibrosis, which progress to invasive malignancy ²⁷. Consensus on this association is lacking, but epidemiological reports have described an increased incidence of lung cancer during idiopathic pulmonary fibrosis follow-up. In addition, lung cancer was found simultaneously with idiopathic pulmonary fibrosis in some autopsy studies ²⁸. The relation between the idiopathic pulmonary fibrosis severity score of – reflected in the number of enlarged lymph nodes – and the emergence of lung cancer also remains uncertain and offers a potential area for further investigation ²⁷.
• Chronic obstructive pulmonary disease (COPD): Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction, inflammation in the airways, and systemic effects or comorbidities ²⁹. Approximately 50% of patients with chronic obstructive pulmonary disease present enlarged hilar and mediastinal lymph nodes. These lymph nodes are located predominantly in the lower paratracheal space, in the aortopulmonary window, and below the carina. Lymph node enlargement is identified more often in patients with signs of severe bronchitis, which seems to be logical because the inflammatory processes seen in chronic bronchitis may result in airway remodeling and narrowing and reactive nodal enlargement. All enlarged lymph nodes in patients with chronic obstructive pulmonary disease have well-defined contours, and most are oval. Neither calcification nor central low attenuation of enlarged lymph nodes is seen in the majority of patients ³⁰.
• Pulmonary embolism. Lymphadenopathy is common in patients with pulmonary arterial hypertension caused by proven chronic pulmonary thromboembolism, and may not necessarily implicate additional pulmonary disease. Enlarged nodes are found on CT in more than one-third of patients with chronic pulmonary thromboembolism with no clinical or radiological evidence of comorbid conditions. The frequent association between enlarged hilar lymph nodes and pleural and pericardial effusions raises the possibility of a common pathophysiological mechanism related to the slowing of lymphatic flow in the mediastinum, caused by increased pressure in the systemic venous system ³¹.
• Drug-induced lymphadenopathy. Hypersensitivity reactions to drugs can cause mediastinal or hilar lymph node enlargement. Anticonvulsants, particularly phenytoin, can cause a pseudolymphoma syndrome with generalized lymphadenopathy in addition to fever, skin rash, eosinophilia, and hepatosplenomegaly. Methotrexate, sulfonamides, penicillin, allopurinol, aspirin, and erythromycin are other examples of drugs with this effect. These reactions tend to follow several months of drug therapy and decrease after discontinuation of the drug ¹⁸.

Bilateral hilar lymphadenopathy treatment

Bilateral hilar lymphadenopathy treatment involves treating the underlying cause.

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