eMedicine Specialties > Pulmonology > Idiopathic Lung Disorders

Lymphomatoid Granulomatosis: Differential Diagnoses & Workup

Author: Nader Kamangar, MD, FACP, FCCP, FAASM,, Associate Professor of Clinical Medicine, Director of Hospitalist/Intensivist Program, Division of Pulmonary, Critical Care and Sleep Medicine, David Geffen School of Medicine at University of California Los Angeles; Associate Director, Combined Pulmonary and Critical Care Fellowship Program, Cedars-Sinai/Olive View-UCLA/West Los Angeles Veterans Affairs Medical Center
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
Contributor Information and Disclosures

Updated: Apr 16, 2009

Differential Diagnoses

Lymphoma, Non-Hodgkin
Sarcoidosis

Other Problems to Be Considered

The differential diagnosis of the clinical and radiological manifestations of lymphomatoid granulomatosis (LYG) is extensive and beyond the scope of this article. When tissue is available for histology, the following 2 groups of diseases need to be differentiated from lymphomatoid granulomatosis:

• Other types of pulmonary granulomatosis
  • Bronchocentric granulomatosis and Churg-Strauss (allergic angiitis and granulomatosis) are characterized by asthma and eosinophilia, which are not features of lymphomatoid granulomatosis.
  • Necrotizing sarcoid granulomatosis has nodular pulmonary sarcoid lesions that mimic lymphomatoid granulomatosis. Unlike lymphomatoid granulomatosis, in necrotizing sarcoid, mediastinal adenopathy often occurs; extrapulmonary disease rarely exists; and histology demonstrating well-formed granulomas with central necrosis also exists.
  • WG, unlike angiitis seen in lymphomatoid granulomatosis, is a true vasculitis with acute and chronic inflammatory cells and vessel destruction. Sinus, upper airway, and renal involvement with necrotizing glomerulonephritis are common in WG but rare in lymphomatoid granulomatosis.
• Other types of malignant lymphoma
  • Hodgkin disease is different because pulmonary involvement without mediastinal adenopathy is rare. The diagnosis requires demonstration of Reed-Sternberg cells.
  • Nasal angiocentric lymphoma (NAL), also known as polymorphic reticulosis or lethal midline granuloma, and lymphomatoid granulomatosis initially were believed to be the same disease, with the former predominantly affecting the upper airway. Recent work has shown that NAL is an EBV-related, natural killer (NK) cell lymphoma and a separate disease entity. Lymphomatoid granulomatosis does not affect the upper airway and nasal passages.
  • Non-Hodgkin lymphoma has well-described pulmonary and extranodal involvement. In particular, peripheral T-cell lymphomas are characterized by vascular infiltration and a degree of morphological heterogeneity. Careful histological diagnosis and studies to determine clonal expansion of T cells are required to rule out lymphomatoid granulomatosis.

Workup

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%)

• 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.

Procedures

• 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.

• Search for CME/CE on This Topic »

• Wegener Granulomatosis (Neurology)

• Waxing and Waning Pulmonary Nodules and Myelodysplastic Syndrome
• Multiple Cranial Neuropathies