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Lymphomatoid Granulomatosis

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

Background

Lymphomatoid granulomatosis (LYG) is a rare Epstein-Barr virus–associated systemic angiodestructive lymphoproliferative disease. It is characterized by prominent pulmonary involvement but can also involve multiple extrapulmonary sites.

Originally described among diseases characterized by pulmonary angiitis and granulomatosis, it mimics Wegener granulomatosis (WG) both clinically and radiographically. However, recent advances have characterized lymphomatoid granulomatosis as a B-cell lymphoma and have provided etiologic insights that may lead to therapeutic advances.

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Pathophysiology

The pathogenesis of lymphomatoid granulomatosis is unknown; however, recent studies have provided overwhelming evidence that lymphomatoid granulomatosis is a distinctive type of malignant lymphoma associated with immunosuppression.[1]

Lymphomatoid granulomatosis was first described as a distinct clinicopathological entity in 1972.[2] The diagnosis is based on the histological triad comprising the following:

  • Nodular polymorphic lymphoid infiltrate composed of small lymphocytes, plasma cells, and variable numbers of large atypical mononuclear cells
  • Angiitis due to transmural infiltration of arteries and veins by lymphocytes (a process distinct from vasculitis in which acute and chronic inflammatory cells are found with associated vessel wall necrosis)
  • Granulomatosis (central necrosis within the lymphoid nodules and not granuloma formation)

Is lymphomatoid granulomatosis a lymphoproliferative disease?

Currently, lymphomatoid granulomatosis generally is considered a B-cell lymphoma associated with an exuberant, benign, T-cell reaction. In the initial description, it was not clear whether lymphomatoid granulomatosis represented a benign process that could progress to lymphoma or a malignant lymphoproliferative disease de novo. By 1990, the disease generally was viewed as an extranodal, angiocentric, T-cell lymphoma with a predilection for the lungs.

Scientific advances using flow cytometry and polymerase chain reaction (PCR) have allowed definitive cell phenotyping and assessment for T-cell receptor and immunoglobulin clonality, the hallmark of hematological malignancy. Surprisingly, these techniques have revealed that in most cases the large atypical cells represent malignant B cells and the T-cell component represents a prominent, polyclonal, reactive, T-cell infiltrate. It is best viewed as a T cell–rich, B-cell lymphoma.

Is lymphomatoid granulomatosis a response to opportunistic infection?

Speculation that lymphomatoid granulomatosis is due to an opportunistic pathogen is fueled by its frequent, though not exclusive, occurrence in patients with various forms of immune dysfunction. It is associated with Sjögren syndrome, chronic viral hepatitis, rheumatoid arthritis, renal transplantation, and human immune deficiency virus (HIV). In addition, a number of patients without associated immune system disorders have T-cell abnormalities.

Recent studies using a combination of PCR and in situ hybridization show that most lymphomatoid granulomatosis cases have malignant B cells containing Epstein-Barr virus (EBV) RNA. The biology of EBV infection involves binding to the complement receptor CD21 on B cells, resulting in the continuous growth or immortalization of infected B cells in vitro. In vivo, polyclonal, B-cell proliferation occurs, but it usually is controlled by immune regulation involving cytotoxic T cells. In immunodeficient states, the host's defenses may be unable to curb EBV-induced B-cell proliferation. In this regard, lymphomatoid granulomatosis shares characteristics with EBV-associated posttransplant lymphoma.

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Epidemiology

Frequency

United States

Lymphomatoid granulomatosis is a rare disease of unknown prevalence.

Mortality/Morbidity

Lymphomatoid granulomatosis usually is progressive and fatal. In the largest studies, mortality rates range from 63-90% at 5 years; however, the clinical course is variable, with reports of prolonged courses and spontaneous remissions.

Race

No known racial predilection exists for lymphomatoid granulomatosis.

Sex

The male-to-female ratio of lymphomatoid granulomatosis is 2:1.

Age

Lymphomatoid granulomatosis is most common after the fifth to sixth decade of life.

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Contributor Information and Disclosures
Author

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.

Coauthor(s)

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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