CONTENTS

• Identification:
  • Lymphadenopathy on chest radiography
  • Lymphadenopathy on CT scan
• Causes of mediastinal and/or hilar lymphadenopathy
• Characterization of lymph nodes
  • Calcified lymph node
  • Low-attenuation lymph node
  • High-attenuation lymph node
• Approach to thoracic lymphadenopathy
• Lymphadenopathy due to specific disorders
  • Sarcoidosis
  • Tuberculosis
• Questions & discussion

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lymphadenopathy on chest radiography

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hilar lymphadenopathy

• Hilar enlargement.
• Abnormal hilar contours.

widened paratracheal stripe

• Normally, the right paratracheal stripe is <4 mm.
• Differential diagnosis of a thickened paratracheal stripe includes: 🌊
  • Paratracheal lymphadenopathy.
  • Pleural effusion.
  • Tracheal malignancy.
  • Lipoma, thyroid malignancy, parathyroid malignancy.
  • Status post esophagectomy with gastric pull through or colonic interposition.

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lymphadenopathy on CT scan

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normal lymph node features

• Ovoid, reniform shape (“kidney shape”).
• Fatty hilum (fat density in the center of the lymph node).
• <1 cm in its smallest diameter.

abnormal lymph node features

• Round rather than ovoid.
• Fatty hilum may be replaced by denser tissue.
• >1 cm in its smallest diameter, but there are some exceptions:
  • For subcarinal lymph nodes, >1.5 cm may be used as a cutoff.
  • Internal mammary, anterior peri-diaphragmatic lymph nodes, and cardiophrenic angle lymph nodes are normally inconspicuous, so any visible nodes in these locations suggests abnormality.(26024596)
• Border may be irregular.

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causes of mediastinal and/or hilar lymphadenopathy

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Mild lymphadenopathy involving only one or two nodal stations is nonspecific, potentially occurring in a wide range of chronic infectious or inflammatory conditions. 

infection

• Mycobacteria:
  • Tuberculosis (primary tuberculosis).
  • Nontuberculous mycobacteria (NTM).
• Fungus:
  • Most frequently:
    • Histoplasmosis.
    • Coccidiomycosis.
  • Less commonly: (32433841)
    • Blastomycosis.
    • Cryptococcus.
• Bacteria (primarily atypical organisms):
  • Tularemia.
  • Yersinia pestis (plague).
  • Anthrax.
  • Psittacosis.
  • Coxiella burnetii (Q fever).
  • Mycoplasma pneumoniae.
• Viral:
  • EBV (Epstein Barr virus).
  • VZV (varicella zoster virus).
  • Influenza H1N1.

malignancy

• Lymphoproliferative disease:
  • Lymphoma.
  • Chronic lymphocytic leukemia (mediastinal > hilar).(34851243)
  • Kaposi sarcoma.
  • Castleman disease.
• Intrathoracic primary cancer (Hilar and mediastinal lymphadenopathy is usually due to an intrathoracic carcinoma – especially lung or breast cancer).(19559225)
  • Lung cancer:
    • SCLC (small cell lung cancer) may cause prominent lymphadenopathy.
    • NSCLC (non-small cell lung cancer).
  • Breast cancer:
    • Autopsy studies suggest that intrathoracic lymph nodes may be involved in most patients.
    • Lymphadenopathy is usually more extensive ipsilateral to the breast cancer. (ERS handbook 3rd ed.)
• Extrathoracic primary cancer:
  • Renal cancer.
  • Thyroid cancer.
  • Esophageal cancer.
  • Colon cancer.
  • Melanoma.
  • Testicular or prostate cancer.

interstitial lung disease

• Sarcoidosis, berylliosis.
• Silicosis, Coal workers pneumoconiosis.
• Amyloidosis. 📖
• Mild lymphadenopathy (e.g., 1-1.5 cm) may be seen with various idiopathic interstitial lung diseases, including:(16641412)
  • Idiopathic pulmonary fibrosis.
  • Connective tissue-related interstitial lung disease.
  • Hypersensitivity pneumonitis.
  • Organizing pneumonia.
  • Chronic eosinophilic pneumonia.

heart failure

medication related (chronic exposure)

• Phenytoin.
• Methotrexate.
• Antibiotics:
  • Erythromycin.
  • Penicillin.
  • Sulfonamides.
• Allopurinol.
• Aspirin. (26860219)

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calcified lymph node

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causes of calcification

• Prior granulomatous disease:
  • Infection (e.g., tuberculosis, histoplasmosis, blastomycosis).
  • Sarcoidosis.
  • Pneumocystis.
• Silicosis, coal workers pneumoconiosis.
• Malignancies:
  • Ovarian carcinoma
  • Colonic adenocarcinoma.
  • Osteosarcoma.
  • Papillary thyroid carcinoma
  • Lung cancer.
  • Lymphoma status post radiation therapy.
• Amyloidosis.(16641412)

dense calcification

• Suggests prior granulomatous disease.
• Differential diagnosis includes:
  • Tuberculosis.
  • Endemic fungal infection (especially histoplasmosis).

peripheral calcification (aka, eggshell calcification)

• Differential diagnosis includes:
  • Silicosis (the classic association).
  • Coal workers pneumoconiosis
  • Sarcoidosis.
  • Histoplasmosis, blastomycosis.
  • Hodgkin's disease, post-irradiation
  • Amyloidosis.

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low-attenuation lymph node

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definition

• Lymph node center has a density below that of skeletal muscle but above fat (about -20 to +20 Hounsfield units).(22520282)

general concepts

• Low attenuation suggests necrosis.
• If a rim of peripheral enhancement is seen, this suggests active granulomatous inflammation.

differential diagnosis of low-attenuation lymph node

• Mycobacteria:
  • Tuberculosis.
  • Nontuberculous mycobacterial infection (especially in the context of HIV/AIDS).
• Histoplasmosis.
• Lymphoma.
• Necrotic metastatic disease, e.g.:
  • Small cell lung carcinoma.
  • Seminoma.
  • Gastric carcinoma.
  • Ovarian carcinoma.
• Whipple disease.
• Crohn disease. (Walker 2019)

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high-attenuation lymph node

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definition

• Lymph node is visibly denser than skeletal muscle (>60 Hounsfield Units).(22520282)
• (These same disorders also demonstrate contrast enhancement.)

differential diagnosis

• Hypervascular metastases:
  • Melanoma.
  • Renal cell carcinoma.
  • Thyroid or parathyroid carcinoma.
  • Kaposi sarcoma.
  • Carcinoid tumor.
  • Hemangioma.
  • Leiomyosarcoma.(22520282)
• Castleman disease.

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approach to thoracic lymphadenopathy

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sorting out tuberculosis vs. sarcoidosis vs. lymphoma

• Anatomic distribution of lymphadenopathy:
  • If asymmetric, this argues against sarcoidosis (≧95% of patients with sarcoidosis have symmetric lymphadenopathy).(31940703) 
  • Predominant location:
    • Sarcoidosis: Hilar > Mediastinal.
    • Lymphoma: Mediastinal > Hilar.
• Symptoms:
  • Lack of constitutional symptoms (e.g., fever, night sweats, weight loss) favors sarcoidosis.
  • If lymphadenopathy is due to lymphoma, usually B-symptoms will occur.
• Clues to the diagnosis of tuberculosis:
  • (1) Rim-enhancing lymph nodes with low-density center.
  • (2) Ipsilateral parenchymal disease in primary tuberculosis.
• Other lymph node characteristics to consider, if present:
  • High-attenuation?
  • Low-attenuation?
  • Calcification?
  • Compression of structures by lymph nodes (usually doesn't occur with sarcoidosis).

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sarcoidosis

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distribution of lymphadenopathy

• Sites of involvement in descending order:
  • Bilateral hilar lymph nodes (95% on CT scan).
  • Right paratracheal lymph node (70%).
  • Aortopulmonary lymph node (~40%).
  • Subcarinal lymph node (25%).
• Garland triad or 1-2-3 sign: Combination of bilateral hilar lymphadenopathy plus right paratracheal lymphadenopathy. This is suggestive of sarcoidosis.
• ⚠️ Suspicious findings:
  • Asymmetrical hilar lymphadenopathy occurs in ~4% of patients with sarcoidosis. This is atypical so it should raise some concern regarding alternative diagnoses (e.g., lymphoma).(31699233)
  • Anterior/prevascular lymphadenopathy or especially posterior/paravertebral lymphadenopathy is infrequent, so this should call into question the diagnosis of sarcoidosis. (26860219)

characteristics of lymph nodes

• Lymph nodes may grow very large (“potato nodes”).
• Lymph nodes tend to grow around bronchi and vasculature, without causing compression. However, bronchial compression is possible (especially involving the right middle lobe).(Walker 2019)
• Calcification eventually develops in ~20% of lymph nodes.
  • Calcification implies chronic sarcoidosis. Calcification is seen in 3% of patients who are five years post-diagnosis, and 20% of patients who are 10 years post-diagnosis. (26860219)
  • Calcification may take various forms (e.g., punctate, amorphous, popcorn, or eggshell).
  • Soft calcifications (faint/cloudy, “icing sugar”) is especially classic for sarcoidosis.
  • Intrathoracic calcification without calcifications involving the spleen or liver may favor sarcoidosis, rather than histoplasmosis.

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tuberculosis

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lymphadenopathy in primary tuberculosis

• Distribution:
  • Distribution of lymphadenopathy is typically asymmetric.
  • Ipsilateral hilar lymphadenopathy is the rule. The right paratracheal and right hilar lymph nodes are typically involved.
  • However contralateral hilar lymphadenopathy and mediastinal lymphadenopathy may also occur (causing bilateral hilar lymphadenopathy in 15%). (28185620)
• Timing & prevalence:
  • Lymphadenopathy is seen in ~40% of adults with primary TB. (26860219)
  • Lymphadenopathy develops within two months.
  • Resolution occurs slowly (often over more than a year).
• CT characteristics:
  • Distinctive rim-enhancement with low-density (necrotic) centers may be seen. Low-density areas correlate with caseous necrosis, implying the presence of active tuberculosis. (Walker 2019) The differential diagnosis of low-density lymph nodes is explored above:📖
  • Enlarged nodes may have a round configuration (unlike normal lymph nodes that are kidney-shaped). (Shepard 2019)
  • Lymphadenopathy is generally accompanied by parenchymal lung involvement.
  • Lymph node calcification may eventually occur in ~1/3 of patients.
• Clinical behavior: Lymph nodes may cause airway obstruction due to external compression (especially involving the right middle lobe, or less frequently the anterior right upper lobe) or frank invasion of the airway. (Shepard 2019) Airway invasion is likely to be initially misdiagnosed as due to malignancy. Eventually healing may occur with residual bronchiectasis. (28185620)

inactive tuberculosis

• Lymph nodes generally appear homogeneous, without low-attenuation areas.(Walker 2019)
• Calcification commonly occurs.

secondary tuberculosis

• Lymphadenopathy is uncommon among immunocompetent patients, occurring in ~5-10% of patients.(Murray 2022; 26860219) Low-attenuation centers may occur, indicative of active disease. (27153783)
• Lymph node calcification reflecting previous primary tuberculosis may remain.

miliary tuberculosis

• Intrathoracic lymphadenopathy may occur.

tuberculosis plus HIV

• When the CD4 count is <200-350/uL, mediastinal lymphadenopathy is more frequent (as opposed to the usual hilar lymphadenopathy).(Shah 2019)

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questions & discussion

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