Lymphomatoid Granulomatosis Workup

• 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.

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.

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.

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.

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.