Lymphomatoid Granulomatosis

Epidemiology

  • First described by Liebow in 1972
  • Mean age: 48 y/o (range: 7-85 y/o)
  • Predisposed groups: M>F (>2:1)
  • Associated with: Lymphoma, Sjogren’s, chronic viral hepatitis, RA, renal transplant

Physiology

  • Pulmonary Vasculitis
    • Angiocentric and angio-destructive infiltration by lymphoblasts/plasma cells, histiocytes/large atypical lymphocytes, mostly T-cells, with abnormal mitotic activity
  • Multi-system angiocentric lymphoproliferative disease of unclear etiology (EBV has been isolated from some lesions)
  • May transform into an aggressive NHL in 15-25% of cases
  • Abnormal T-cell function with monoclonal T-cell proliferation: has been demonstrated
    • Primary T-cell lymphomas (due to HTLV-I) can produce a syndrome like lymphomatoid granulomatosis

Pathologic Patterns

  • Destructive inflammatory granulomatous angiitis with lymphoid infiltrate (with atypical and immature cells with abundant mitoses/ paucity of PMN and eosinophils)

Diagnosis

  • PFT’s: decreased DLCO/ increased Vd/Vt ratio
  • ABG: elevated A-a gradient
  • CXR: resembles Wegener’s
  • Upper airway Bx: diagnostic
  • OLB: may be neccesary for diagnosis
  • CXR/Chest CT patterns: pulmonary lesions usually wax-and-wane with new lesions appearing while others regress/ hilar and mediastinal nodes are rarely present
    • Fluffy nodular infiltrates/lung nodules (most common pattern): lower-lobe predilection (usually peripheral, may coalesce)
      • May be cavitary
      • May produce large mass lesions
    • Endobronchial lesions: have been reported in some cases (bronchioles>lobar bronchi), may produce obstruction
  • CBC: usually normal
  • Dysproteinemia: usually absent

Clinical

Upper Airway Manifestations

Pulmonary Manifestations

  • Epidemiology: usually present
  • Clinical
    • Chest pain
    • Dyspnea
    • Cough
    • Pulmonary Hypertension (see Pulmonary Hypertension, [[Pulmonary Hypertension]]): due to pulmonary vasculitis
    • Pneumonia-like illness: presents with dyspnea/ cough/ sputum
    • Endobronchial lesion: obstructive symptoms/ hemoptysis (may be massive)
    • Pneumothorax:

CNS Manifestations

  • Epidemiology: 25% of cases
  • Seizures/ asymmetric focal deficits

Dermatologic Manifestations

  • Epidemiology: 50% of cases
  • Patchy erythematous or papular rash (usually small, confluent and on the extremities)/ ulcerations/ subcutaneous nodules

Renal Mnaifestations

  • Clinical involvement is uncommon (despite autopsy evidence of GLN)
  • Clinical involvement is rare but autopsy involvement (focal necrosis and proliferative lesions without GLN) is common

Other Manifestations

  • Hepatic (unusual): involvement worsens prognosis
  • Lymph node/ spleen (rarely involved): involvement does not affect prognosis
  • Nasopharynx and upper airways (rarely involved, in contrast to Wegener’s)
  • Other: fever/ malaise
  • Aggressive Lymphoma: occurs in 15-25% of cases

Treatment

Asymptomatic Disease

  • Some patients do not require treatment (due to slowly progressive disease)

Symptomatic Disease

  • Steroids + Cytoxan
    • Responsive but recurrence/ refractory disease is frequent (and high-grade NHL complicates some cases)
    • Better long-term response with minimal disease and lack of CNS disease
    • 50% of all patients receiving qOD steroids + Cytoxan had average survival of 4 years
  • XRT
    • Useful for localized lesions

Prognosis

  • Median survival is 17 months (despite treatment)/ death due to CNS or lung involvement
  • Virtually all patients that did not achieve remission developed lymphomas
  • >50% of patients die within first 5 years
  • Death may occur due to CNS etiology/ respiratory etiology (hemoptysis)/ progressive NHL

References

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