Can Lymphoid Interstitial Pneumonia (LIP) present with lymphadenopathy and cystic changes in the lungs?

Can LIP Present with Lymph Nodes and Cysts?

Yes, Lymphoid Interstitial Pneumonia (LIP) characteristically presents with pulmonary cysts on HRCT, and when lymphadenopathy is present, it should raise immediate concern for lymphomatous transformation or underlying Sjögren's syndrome.

Cystic Changes in LIP

Cyst formation is a recognized and common feature of LIP on high-resolution CT imaging. The 2013 ATS/ERS classification explicitly acknowledges that some cases of LIP show striking cyst formation on HRCT 1. These cysts have specific characteristics:

• Cysts are present in up to 80% of LIP patients and are typically few in number, measuring less than 3 cm in diameter 2
• The cysts are thin-walled and scattered throughout the lungs 2
• They typically occur in peribronchovascular and subpleural distributions 1
• The cysts are usually less than 1 cm in size when associated with underlying conditions 1

Lymphadenopathy: A Critical Warning Sign

The presence of mediastinal lymphadenopathy in LIP is NOT a typical feature and should immediately trigger investigation for lymphoma. According to diagnostic guidelines:

• Pleural effusion or mediastinal adenopathies should raise suspicion of low-grade lymphoma and requires thorough investigation 3
• In Sjögren's patients with LIP, lymphadenopathy accompanied by cystic lesions may indicate MALT lymphoma with focal amyloidosis 1
• Lymphadenopathy, growing lung nodules, and/or progressive cystic lung disease warrant biopsy in Sjögren's patients 1

Clinical Context Matters

The presence of lymphadenopathy requires immediate assessment for:

• Lymphomatous transformation: Approximately 5% of LIP cases evolve into lymphoma 3, 4
• Underlying Sjögren's syndrome: Focal lung nodules and consolidations are present in approximately one-third of Sjögren's patients with pulmonary lymphoma versus only 3% without lymphoma 1
• PET-avid parotitis (standardized uptake value ≥ 4.7) accompanied by lung nodules is particularly concerning 1

Diagnostic Algorithm When Both Features Present

When encountering a patient with suspected LIP showing both cysts and lymphadenopathy:

1. Immediately investigate for lymphoma with PET scan if nodules exceed 8 mm, consolidations are present, or lymphadenopathy is identified 1

2. Screen for underlying autoimmune disease, particularly Sjögren's syndrome:

   • Serum protein electrophoresis 3
   • Anti-SSA/SSB antibody testing 3
   • HIV serology 3
   • Screening for other autoimmune diseases 3

3. Consider biopsy for lymphadenopathy, growing nodules, or progressive cystic disease 1

4. Clinical observation may be appropriate only for incidental subcentimeter nodules, stable cysts, and isolated PET-negative subcentimeter lymphadenopathy 1

Critical Pitfalls to Avoid

• Do not assume lymphadenopathy is benign in LIP—it is atypical and warrants aggressive investigation 3
• Do not delay multidisciplinary review involving rheumatology, pulmonology, pathology, radiology, and hematology/oncology when neoplasm is suspected 1
• Regular radiological and clinical surveillance is essential to detect lymphomatous transformation, given the 5% risk 3
• Be aware that extensive cystic disease can be the predominant finding in some cases, though this is uncommon 2

The combination of cysts with lymphadenopathy represents a higher-risk presentation that demands thorough evaluation to exclude malignancy, particularly in the context of Sjögren's syndrome or other immune dysregulation 1, 3.