Lymphoid interstitial pneumonia (LIP) is a rare benign lymphoproliferative disorder of the lung characterized by diffuse polyclonal infiltration of the pulmonary interstitium, alveolar walls, and septa by mature lymphocytes, plasma cells, and macrophages. It is one of the lymphoid lesions of the lung defined by the WHO and ATS/ERS classifications and was historically classified as an idiopathic interstitial pneumonia (now considered secondary to immunological abnormalities in most cases).
LIP is most commonly secondary to underlying immunological diseases. Sjögren syndrome accounts for 25% of cases (LIP is the most common interstitial lung disease pattern in primary Sjögren). Other associations include common variable immunodeficiency (CVID, accounting for granulomatous-lymphocytic interstitial lung disease — GLILD), HIV infection (LIP is an AIDS-defining illness in children but also occurs in HIV-infected adults), systemic lupus erythematosus, rheumatoid arthritis, Castleman disease, multicentric autoimmune cytopenias, Hashimoto thyroiditis, autoimmune hepatitis, and EBV. Idiopathic LIP is rare in modern series.
Patients present with subacute progressive dyspnea, dry cough, fatigue, and constitutional symptoms over months. Pulmonary function tests show restrictive pattern with reduced DLCO. High-resolution CT shows diffuse bilateral ground-glass opacities with characteristic features: thin-walled perivascular cysts (60-80% — virtually pathognomonic in correct context), centrilobular nodules, interlobular septal thickening, and patchy consolidation. Definitive diagnosis requires surgical lung biopsy (transbronchial biopsy is usually inadequate) showing dense polyclonal lymphoplasmacytic infiltrate distributed along bronchovascular bundles, septa, and pleura without architectural distortion (distinguishing from lymphoma). Immunohistochemistry confirms polyclonality (kappa/lambda ratio normal). Treatment includes systemic corticosteroids (prednisone 0.5-1 mg/kg/day) tapered over months, with steroid-sparing immunosuppressives (azathioprine, mycophenolate) for refractory cases. Rituximab has shown benefit, particularly in CVID-GLILD. Treatment of underlying disease (HIV antiretrovirals, Sjögren management, immunoglobulin replacement in CVID) is critical. Prognosis is variable; 33-50% achieve clinical remission, while some progress to fibrosis or transform to MALT lymphoma (5%), requiring long-term follow-up with serial imaging.