Honeycombing

Jeffrey P. Kanne, MD

DIFFERENTIAL DIAGNOSIS

Common

Usual Interstitial Pneumonia (UIP)
Nonspecific Interstitial Pneumonia (NSIP)
Chronic Hypersensitivity Pneumonitis

Less Common

Sarcoidosis
Asbestosis

Rare but Important

Acute Interstitial Pneumonia

ESSENTIAL INFORMATION

Key Differential Diagnosis Issues

Honeycombing represents end-stage lung fibrosis
- As final common pathway, can be difficult to distinguish inciting cause
- Honeycombing seen on CT (macroscopic) does not always correlate with microscopic honeycombing seen on histology
- Poor prognostic indicator
Characterized on imaging by
- Clustered cysts with well-defined walls
- 3-10 mm in diameter (up to 2.5 cm), similar size
- Frequently form stacked rows in peripheral lung
- Cystic spaces on occasion can become large
Honeycombing always associated with other findings of lung fibrosis

Helpful Clues for Common Diagnoses

Usual Interstitial Pneumonia (UIP)
- Histologic pattern of interstitial fibrosis characterized by
  - Temporal and spatial heterogeneity
  - Patchy distribution
  - Subpleural and basal predominance
  - Fibroblastic foci
- Most patients with histologic and CT pattern of UIP have idiopathic pulmonary fibrosis (IPF)
- Other causes of UIP pattern
  - Collagen-vascular disease, especially rheumatoid arthritis
  - Drug toxicity
  - Asbestosis
  - Hypersensitivity pneumonitis
  - Familial fibrosis
  - Inflammatory bowel disease (rare)
- Most common cause of honeycombing
- Early honeycombing forms in subpleural lung
  - Basal predominance
  - Clusters and rows of honeycomb cysts
- Other associated features of lung fibrosis
  - Reticulation
  - Traction bronchiectasis and bronchiolectasis
  - Architectural distortion
  - Ground-glass opacity less than extent of reticular abnormality
Nonspecific Interstitial Pneumonia (NSIP)
- Histological pattern of interstitial fibrosis characterized by
  - Spatial and temporal homogeneity
  - Basal predominant
  - Cellular, mixed, and fibrotic forms
- Most patients have collagen vascular disease (especially scleroderma, mixed connective tissue disease, and polymyositis) or hypersensitivity pneumonitis
- Other causes of NSIP pattern
  - Idiopathic (young women of east Asian ethnicity)
  - Drug toxicity
  - Familial fibrosis
  - Cigarette smoking (rare cause)
- Honeycombing on CT is a late finding; less common with NSIP than UIP
- Associated features
  - Basal predominant ground-glass opacity (most common)
  - Superimposed reticulation
  - Traction bronchiectasis and bronchiolectasis
  - Subpleural sparing (suggestive of diagnosis)
  - Peripheral and peribronchovascular distribution
  - Esophageal dilation (scleroderma and mixed connective tissue disease)
Chronic Hypersensitivity Pneumonitis
- Lung fibrosis resulting from chronic hypersensitivity reaction to organic antigen or low-molecular-weight inorganic compounds
  - Mold and avian antigens most common causes
  - Inorganic compounds include isocyanates (industrial paints)
- Honeycombing infrequent
- Associated features
  - Peripheral and peribronchial reticulation
  - Traction bronchiectasis and bronchiolectasis
  - Architectural distortion
  - Patchy ground-glass opacity
  - Lobular foci of air-trapping (very suggestive of diagnosis)
  - Poorly defined centrilobular nodules (very suggestive of diagnosis)
  - Extreme lung bases typically spared in contrast to idiopathic pulmonary fibrosis

Helpful Clues for Less Common Diagnoses

Sarcoidosis
- Honeycombing less common in sarcoidosis than with other end-stage lung diseases
- Honeycomb cysts typically larger than those occurring with usual interstitial pneumonia
- Subpleural and MID and UPPER lung zone distribution with basal sparing
- Lymphadenopathy uncommon with end-stage sarcoidosis
Asbestosis
- Interstitial fibrosis from asbestos exposure
  - Histologically similar to UIP
- Subpleural branching opacities (fibrosis centered on respiratory bronchioles where asbestos fibers deposited) earliest finding on CT
- Honeycombing less common unless disease severe
- Associated features
  - Parenchymal bands and subpleural curvilinear opacities
  - Calcified or noncalcified pleural plaques
  - Subpleural reticulation
  - Traction bronchiectasis and bronchiolectasis
  - Architectural distortion

Helpful Clues for Rare Diagnoses

Acute Interstitial Pneumonia
- Acute, rapidly evolving illness with respiratory failure requiring ventilatory support
  - 50% mortality rate
  - Idiopathic acute respiratory distress syndrome (ARDS)
  - Characterized histologically by diffuse alveolar damage
- Predominant radiographic features
  - Consolidation (basal and posterior lungs)
  - Ground-glass opacity (superior and anterior lungs)
- Honeycombing late finding in survivors
  - More common in anterior lung due to barotrauma (overinflating nondependent alveoli)