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Lymphomatoid Granulomatosis Workup

  • Author: Nader Kamangar, MD, FACP, FCCP, FCCM; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
Updated: Dec 31, 2015

Laboratory Studies

No characteristic laboratory abnormalities exist in lymphomatoid granulomatosis.

  • Obtain a WBC count.
    • Leukopenia (20%) and lymphopenia (33%) may be present.
    • CD4 lymphocyte count may be low.
    • Leukocytosis greater than 10,000 cells/μ L is rare.
  • Hematocrit is normal or slightly elevated.
  • Erythrocyte sedimentation rate (ESR) has mild-to-moderate elevation but may be normal.
  • Obtain renal and liver function studies. Findings are usually normal.
  • Urinalysis results are usually normal.
  • Delayed-type hypersensitivity and lack of anergy have been reported in more than 50% of cases.

Imaging Studies

Obtain chest radiographs. Results are usually abnormal but nonspecific. The radiologic differential diagnosis for lymphomatoid granulomatosis includes pseudolymphoma, malignant lymphoma, lymphocytic interstitial pneumonia, metastasis, sarcoidosis, Wegener granulomatosis, and cryptogenic organizing pneumonia. Some lesions regress, while others progress. Chest radiograph lesions and abnormalities include the following:

  • Bilateral nodules or masses in the lower and peripheral lung fields (80-100%). These nodules may occasionally be migratory in nature.
  • Pleural effusions (33%)
  • Pneumonitis or large masslike lesion (30%)
  • Cavitation of nodules (30%)
  • Pneumothorax (5%)

See the image below.

Chest radiograph showing a dense, large, right upp Chest radiograph showing a dense, large, right upper lobe masslike infiltrate and bilateral nodular disease.

Hilar and mediastinal lymphadenopathy are rare and should prompt consideration of an alternative diagnosis or raise concern of transformation into aggressive lymphoma. Airway disease can involve the following:

  • Distal small airway
  • Main bronchial disease (occasionally)
  • Atelectasis or lobar collapse on chest films

Radiographic differential diagnoses can include the following:

  • Primary pulmonary and metastatic malignancy
  • Granulomatous diseases, including WG and sarcoidosis
  • Eosinophilic granulomatosis
  • Amyloidosis

Perform a chest CT scan. The role of CT scan requires further study. CT scan better defines pulmonary lesions, but findings are nonspecific. CT scan is useful for monitoring disease progression and response to treatment.

See the images below.

Contrast-enhanced chest CT scan showing poorly def Contrast-enhanced chest CT scan showing poorly defined nodular peribronchovascular infiltrates with air-bronchograms.
Contrast-enhanced chest CT scan showing poorly def Contrast-enhanced chest CT scan showing poorly defined nodular peribronchovascular infiltrates with air-bronchograms.

Perform brain imaging. CT scan shows high-density lesions. MRI lesions are isointense or hyperintense on T1-weighted images and hyperintense on T2-weighted images. Enhancement may be punctate and linear, a finding that can be relatively specific for inflammation of deep cerebral vessels.



Perform a tissue diagnosis.

  • In general, perform a biopsy on the most accessible organ involved.
  • Establishing the diagnosis of lymphomatoid granulomatosis usually requires an open lung or video-assisted thoracoscopic biopsy. Transbronchial lung biopsy has not been studied rigorously. Because of the focal nature of lymphomatoid granulomatosis and the fact that it is not bronchocentric, a low diagnostic yield with bronchoscopic transbronchial biopsies is likely. In one study, the diagnosis was established with the aid of open lung biopsy in 70% of cases, bronchoscopic lung biopsy in 15% of cases, and extrapulmonary biopsy in 15% of cases. In cases where bronchoscopic lung biopsy is nondiagnostic, a thoracoscopic lung biopsy may be necessary.
  • Skin biopsy is the least invasive.
  • In all cases, inform the pathologist that lymphomatoid granulomatosis is clinically suspected to ensure that appropriate studies are performed.

Histologic Findings

A definitive diagnosis of lymphomatoid granulomatosis requires the presence of the following histological triad:

  • Polymorphic lymphocytic infiltrate
  • Angiitis
  • Granulomatosis (central necrosis)

A nodular perivascular infiltrate containing plasma cells, lymphocytes, and large atypical mononuclear cells in various stages of maturity is present. This is a destructive lesion due to vessel occlusion by lymphocytic infiltration and subsequent tissue necrosis.

Perform analysis for cell phenotype, clonality, and EBV infection. As discussed above, despite the predominance of T cells, the malignant cells appear to be B cells, and the T-cell infiltrate is polyclonal (see Pathophysiology). In general, the B-cell population is clonally expanded; however, oligoclonal populations have been identified in rare cases. A similar finding is described in posttransplant lymphoma and probably reflects an EBV-related phenomenon.

When peripheral nerve involvement exists, the infiltrate surrounds the nerve and causes spotty demyelination.

Contributor Information and Disclosures

Nader Kamangar, MD, FACP, FCCP, FCCM Professor of Clinical Medicine, University of California, Los Angeles, David Geffen School of Medicine; Chief, Division of Pulmonary and Critical Care Medicine, Vice-Chair, Department of Medicine, Olive View-UCLA Medical Center

Nader Kamangar, MD, FACP, FCCP, FCCM is a member of the following medical societies: Academy of Persian Physicians, American Academy of Sleep Medicine, American Association for Bronchology and Interventional Pulmonology, American College of Chest Physicians, American College of Critical Care Medicine, American College of Physicians, American Lung Association, American Medical Association, American Thoracic Society, Association of Pulmonary and Critical Care Medicine Program Directors, Association of Specialty Professors, California Sleep Society, California Thoracic Society, Clerkship Directors in Internal Medicine, Society of Critical Care Medicine, Trudeau Society of Los Angeles, World Association for Bronchology and Interventional Pulmonology

Disclosure: Nothing to disclose.


Anthony W O'Regan, MD Clinical Lecturer of Medicine, Department of Internal Medicine, Section of Respiratory Medicine, National University of Ireland, Galway; Adjunct Professor of Medicine, Boston University Medical Center

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD, FACP, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society

Disclosure: Nothing to disclose.

Additional Contributors

Ryland P Byrd, Jr, MD Professor of Medicine, Division of Pulmonary Disease and Critical Care Medicine, James H Quillen College of Medicine, East Tennessee State University

Ryland P Byrd, Jr, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

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Chest radiograph showing a dense, large, right upper lobe masslike infiltrate and bilateral nodular disease.
Contrast-enhanced chest CT scan showing poorly defined nodular peribronchovascular infiltrates with air-bronchograms.
Contrast-enhanced chest CT scan showing poorly defined nodular peribronchovascular infiltrates with air-bronchograms.
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