Kevin O. Leslie, MD, Mayo Clinic, Scottsdale, Arizona Tomographic Pathology of the Lung Kevin O. Leslie, MD, Mayo Clinic, Scottsdale, Arizona A field guide to HRCT patterns of diffuse lung disease

The CT Patterns of Pulmonary Disease Alveolar Filling Interstitial cells/ protein Neutrophils Lymphocytes Edema Neutrophils Macrophages Edema/fibrin Hemorrhage/Fibrin/protein Fibroblasts Interstitial fibrosis (mild) Organizing pneumonia (any cause) Alveolar Filling Interstitial cells/ protein Neutrophils Lymphocytes Edema Neutrophils Macrophages Edema/fibrin Hemorrhage/Fibrin/protein Fibroblasts Interstitial fibrosis (mild) Organizing pneumonia (any cause) Alveolar Filling Interstitial cells/ protein Neutrophils Lymphocytes Edema Neutrophils Macrophages Edema/fibrin Hemorrhage/Fibrin/protein Fibroblasts Interstitial fibrosis (mild) Organizing pneumonia (any cause) Alveolar Filling Interstitial cells/ protein Neutrophils Lymphocytes Edema Neutrophils Macrophages Edema/fibrin Hemorrhage/Fibrin/protein Fibroblasts Interstitial fibrosis (mild) Organizing pneumonia (any cause)

Rationale Gross anatomy is the foundation science of pathology. Pathologists are comfortable with gross anatomy. The CT scan is a reasonable approximation of gross lung anatomy.

Qual es su Diagnostico? LAM UIP Langerhans Proteinosis DIP

Qual es su Diagnostico? LAM UIP Langerhans Proteinosis DIP

Qual es su Diagnostico? LAM UIP Langerhans Proteinosis DIP

Objectives Part I: Normal CT anatomy Part II: Differential diagnosis by pattern Part III: Differential diagnosis by distribution and anatomic location

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1). What microscopic anatomy of the lung is visible on CT scan?

Normal lung on HRCT Bronchovascular bundles 8mm 8mm

CENTER OF LOBULE

The Lung Lobules

What CAN we see on the lung HRCT scan? Opacities down to about 2 mm in size (2000 microns!) Septa around secondary lobules and bronchovascular bundles within secondary lobules -especially when abnormal. Differences in tissue density and vascularity

Normal Anatomy on HRCT Arteries and airways travel together 2. Arteries and airways of equal size 3. Bronchi visible in medial half of lung- straight walls that taper 4. Veins travel separately Slide courtesy J. Muhm MD

Objectives Part I: Normal CT anatomy Part II: Differential diagnosis by pattern Part III: Differential diagnosis by distribution and anatomic location

HRCT- Patterns Ground Glass Consolidation Reticular and linear densities Nodular Opacities Mosaic pattern Cystic

6 Pathology Patterns of Pulmonary Disease 4 CT Patterns of Pulmonary Disease 1. Acute lung injury Acute lung injury Clinical Evolution is Critical ! Delicate alveolar wall fibrosis can produce GG ! Ground Glass and Consolidation 1. 2. Fibrosis Cellular infiltrates 3. Cellular infiltrates Alveolar filling Fibrosis/ honeycombing 2. 4. Alveolar filling Fibrosis 5. Nodules 3. Nodules/masses Nodules 6. Minimal changes 4. Airtrapping + cysts Minimal changes

Radiologic Pattern 1. - Acute lung injury. - Cellular infiltrates Radiologic Pattern 1 - Acute lung injury - Cellular infiltrates - Alveolar filling These patterns are all characterized by varying degress of: Ground glass infiltrates +/- consolidation DDX for “consolidation” Infection Neoplasm Infarct Sarcoidosis Localized Scar(s) Wegener Granulomatosis Ground glass infiltrates = hazy attenuation w/airways and arteries/veins still visible through it Consolidation = Opacification of lung parenchyma obscuring underlying detail

Cryptogenic Organizing Pneumonia Desquamative Interstitial Pneumonia DDX for Ground Glass DAD Alveolar Filling Neutrophils Edema Macrophages Hemorrhage Fibrin/protein Fibroblasts Organizing pneumonia (any cause) Interstitial Material Lymphocytes edema/fibrin Interstitial fibrosis When mild FIBRIN COP FIBROBLASTS DIP MACROPHAGES Mild interstitial fibrosis Cryptogenic Organizing Pneumonia DAD/ARDS Desquamative Interstitial Pneumonia

Ground-glass with a secondary pattern Alveolar Proteinosis Crazy Paving Ground-glass with sharply demarcated areas of sparing Smooth reticulation

Importance of Evolution for GG Eosinophilic pneumonia

4 CT Patterns of Pulmonary Disease Ground Glass and Consolidation Ground Glass and consolidation Alveolar Filling Interstitial cells/ protein Neutrophils Lymphocytes Edema Neutrophils Macrophages Edema/fibrin Hemorrhage/Fibrin/protein Fibroblasts Interstitial fibrosis (mild) Organizing pneumonia (any cause)

Fibrosis Radiologic Pattern 2 These patterns are all characterized by varying degrees of: Linear opacities Reticular opacities - with or without honeycomb cysts

Differential diagnosis for diffuse reticulation on HRCT UIP “Fibrotic” NSIP All connective tissue diseases Chronic hypersensitivity pneumonitis Asbestosis PLCH (late) Some chronic drug reactions Erdheim Chester Disease Hermansky-Pudlak Syndrome

Erdheim Chester Disease (Non-Langerhans cell histiocytosis)

UIP Mimic- Asbestosis march

NSIP/Fibrotic

Differential diagnosis for fibrosis with HONEYCOMB CYSTS on HRCT UIP/IPF (mainly) Less commonly: Connective tissue diseases Chronic hypersensitivity pneumonitis Asbestosis

Example: Rheumatoid Arthritis Right Lung transplant- RA changes on left, khouma

Traction bronchiectasis -A sign of fibrosis

4 CT Patterns of Pulmonary Disease Fibrosis Ground Glass and consolidation Fibrosis Alveolar Filling Interstitial cells/ protein Neutrophils Lymphocytes Edema Neutrophils Macrophages Edema/fibrin Hemorrhage/Fibrin/protein Fibroblasts Interstitial fibrosis (mild) Organizing pneumonia (any cause) Alveolar Filling Interstitial cells/ protein Neutrophils Lymphocytes Edema Neutrophils Macrophages Edema/fibrin Hemorrhage/Fibrin/protein Fibroblasts Interstitial fibrosis (mild) Organizing pneumonia (any cause)

Nodules/masses Radiologic Pattern 3 These patterns are all characterized by rounded opacities - Large or small - Single or numerous

Sarcoidosis Thickened bronchovascular bundles with nodularity Confluence of nodules – larger opacities Fibrosis leads to distortion of the lung architecture and traction bronchiectasis

Radiologic Pattern 3: Nodules/masses Exogenous lipoid pneumonia

Subacute Hypersensitivity Pneumonitis CT Findings Micronodules Ground glass Distribution Diffuse Lobular anatomy Centrilobular nodularity

Subacute clinical course MAC Hot Tub-Hypersensitivity pneumonitis

Chronic clinical course Silicatosis! Chronic clinical course

Muhm’s Nodules “Pearl” When multiple nodules are present: Similar size = More likely infection Widely different sizes More likely neoplasm

4 CT Patterns of Pulmonary Disease Nodules Ground Glass and consolidation Fibrosis Alveolar Filling Interstitial cells/ protein Neutrophils Lymphocytes Edema Neutrophils Macrophages Edema/fibrin Hemorrhage/Fibrin/protein Fibroblasts Interstitial fibrosis (mild) Organizing pneumonia (any cause) Alveolar Filling Interstitial cells/ protein Neutrophils Lymphocytes Edema Neutrophils Macrophages Edema/fibrin Hemorrhage/Fibrin/protein Fibroblasts Interstitial fibrosis (mild) Organizing pneumonia (any cause) Nodules Alveolar Filling Interstitial cells/ protein Neutrophils Lymphocytes Edema Neutrophils Macrophages Edema/fibrin Hemorrhage/Fibrin/protein Fibroblasts Interstitial fibrosis (mild) Organizing pneumonia (any cause)

Mosaic patterns and Cysts Radiologic Pattern 4 Mosaic patterns and Cysts These patterns are characterized by differences in lobular attenuation (mosaic) or cyst formation - Large or small - Single or numerous

Inspiratory HRCT Expiratory HRCT Mosaic Perfusion

Lymphangioleiomyomatosis (LAM) Diseases with Cysts Lymphangioleiomyomatosis (LAM) Scattered thin-walled cysts Intervening normal lung Uniform distribution- All lobes involved Sometimes can be difficult to distinguish from emphysema Similar to Langerhans histiocytosis but without upper lung zone restriction

Lymphangioleiomyomatosis (LAM)

Langerhans cell histiocytosis

4 CT Patterns of Pulmonary Disease Mosaic patterns and cysts Ground Glass and consolidation Fibrosis Alveolar Filling Interstitial cells/ protein Neutrophils Lymphocytes Edema Neutrophils Macrophages Edema/fibrin Hemorrhage/Fibrin/protein Fibroblasts Interstitial fibrosis (mild) Organizing pneumonia (any cause) Alveolar Filling Interstitial cells/ protein Neutrophils Lymphocytes Edema Neutrophils Macrophages Edema/fibrin Hemorrhage/Fibrin/protein Fibroblasts Interstitial fibrosis (mild) Organizing pneumonia (any cause) Nodules Mosaic patterns and cysts Alveolar Filling Interstitial cells/ protein Neutrophils Lymphocytes Edema Neutrophils Macrophages Edema/fibrin Hemorrhage/Fibrin/protein Fibroblasts Interstitial fibrosis (mild) Organizing pneumonia (any cause) Alveolar Filling Interstitial cells/ protein Neutrophils Lymphocytes Edema Neutrophils Macrophages Edema/fibrin Hemorrhage/Fibrin/protein Fibroblasts Interstitial fibrosis (mild) Organizing pneumonia (any cause)

Objectives Part I: Normal CT anatomy Part II: Differential diagnosis by pattern Part III: Differential diagnosis by distribution and anatomic location

Part III: Common anatomic distributions in diffuse lung disease Upper lobe: Inhalational disease/Sarcoid Lower lobe: Arterial and lymphatic diseases Middle lobe(s) (incl. lingula): Post obstructive disease Peripheral: Drug toxicity (e.g. bleo), eosinophilic pneumonia, UIP, NSIP, COP Central: edema, ARDS

Diseases that involve the airways- typically inhalational

Airway-centered pathology as a reflection of inhalational disease Infections Aspiration Hypersensitivity pneumonitis Respiratory bronchiolitis interstitial lung disease Langerhans cell histiocytosis Pneumoconioses Smoking-related diseases

Lymphatic-associated patterns reflect specific diseases Sarcoidosis Lymphomas Lymphangitic carcinomatosis

Sarcoidosis following lymphatic routes

Lymphangitic Carcinoma

Cystic patterns reflect specific diseases Langerhans cell histiocytosis Lymphangioleiomyomatosis

Nearly unique HRCT in Langerhans cell histiocytosis

Lymphangioleiomyomatosis/LAM HMB45 Lymphangioleiomyomatosis/LAM

Pattern Distribution Changes over time CONCLUSION There is good correlation between HRCT and lung histopathology in a number of diffuse lung diseases Pattern Distribution Changes over time Tomar la prueba….

Qual es su Diagnostico? LAM UIP Langerhans Proteinosis DIP

Qual es su Diagnostico? LAM UIP Langerhans Proteinosis DIP

Qual es su Diagnostico? LAM UIP Langerhans Proteinosis DIP

The 4 CT Patterns of Pulmonary Disease Questions? Ground Glass and consolidation Fibrosis Nodules Mosaic patterns and cysts Alveolar Filling Interstitial cells/ protein Neutrophils Lymphocytes Edema Neutrophils Macrophages Edema/fibrin Hemorrhage/Fibrin/protein Fibroblasts Interstitial fibrosis (mild) Organizing pneumonia (any cause) The 4 CT Patterns of Pulmonary Disease