Part 2: Case Studies

A Pattern-Based Approach to Interstitial Lung Disease Part 2: Case Studies Kevin O. Leslie, M.D. Consultant and Professor Department of Pathology and Laboratory Medicine Mayo Clinic Arizona

The 6 Patterns of Interstitial Lung Disease 1. Acute Injury Prototype: DAD 2. Fibrosis Prototype: UIP 3. Cellular Interstitial Prototype: HSP 4. Alveolar Filling Prototype: OP 5. Nodules Prototype: Sarcoidosis 6. Minimal Changes Prototype: SAD

Differential diagnosis

remember the mixed patterns! Not infrequently, combinations of patterns may occur. For example, Acute Lung Injury (Pattern 1) -with hyaline membranes, may coincide with Airspace Filling (Pattern 4) -with organizing pneumonia. In some instances, this is an expected part of a disease natural history, while in others, combined features may actually represent two unrelated, or marginally related, diseases intersecting or colliding.

The 4 CT Patterns of Pulmonary Disease Ground Glass and Consolidation GGO Consolidation Without HC cysts Alveolar Filling Interstitial Material Infection Peripheral Neutrophils Lymphocytes Neoplasms NSIP Edema Neutrophils CVD Macrophages Edema/fibrin Chr Drug Chr HP Hemorrhage Interstitial fibrosis UIP (early) Fibrin/protein Organizing pneumonia Fibroblasts Reticulation with Distortion With HC Cysts UIP CVD Local Scar Nodules Mosaic patterns and cysts Neoplasms Infections Subacute HP RB-ILD Focal OP PLCH Sarcoidosis Certain Drugs Rheumatoid nodules PHT PVOD LAM Constrictive Bronch PLCH Emphysema 18

A Pattern-Based Approach to Lung Disease Kevin O. Leslie. MD Case 1

A Pattern-Based Approach to Lung Disease Clinical history A 18-year-old high school student, captain of the junior varsity track and field team, presents with one week of rapidly progressive shortness of breath accompanied by night sweats and fever. He is hospitalized and requires intubation. Chest imaging shows bilateral asymmetrical ground-glass opacities.

The biopsy Shows

A Pattern-Based Approach to Lung Disease What is the pattern? 1. Acute injury 2. Fibrosis 3. Cellular infiltrates 4. Alveolar filling 5. Nodules 6. Minimal changes

The 6 Patterns of Interstitial Lung Disease 1. Acute Lung Injury - with hyaline membranes? - with eosinophils? - with necrosis? - with siderophages? 2. Fibrosis - with temporal heterogeneity? - with honeycombing? - with diffuse fibrosis? - with pleuritis? 3. Cellular Infiltrates - with lymphocytes and plasma cells? - with neutrophils? - with granulomas? - with focal organization? - with pleuritis? 4. Alveolar Filling - with macrophages? - with neutrophils? - with organizing pneumonia? - with eosinophilic material? - with hemorrhage? 5. Nodules - with granulomas? - with lymphoid tissue? - with necrosis? - with atypical cells? - with stellate scars? - with organizing pneumonia? 6. Minimal Changes - with small airways disease? - with vascular changes? - with cysts? - sampling problem?

A Pattern-Based Approach to Lung Disease What is your favored diagnosis? 1. Acute granulomatous infection 2. Churg-Strauss Syndrome 3. Acute viral pneumonitis 4. Eosinophilic pneumonia 5. Cryptogenic organizing pneumonia

A Pattern-Based Approach to Lung Disease Case 2

A Pattern-Based Approach to Lung Disease Clinical history A 28-year-old woman from Las Vegas presents with constitutional symptoms, including shortness of breath, fatigue, and nonproductive cough. The physical exam is remarkable for palmar erythema and slight periorbital edema.

A Pattern-Based Approach to Lung Disease CT Chest Chest imaging shows bilateral ground-glass opacities accompanied by mild reticulation. The lower lung zones are primarily involved and most consistently with a peripheral distribution. Very slight subpleural sparing is noted.

The histopathology shows

A Pattern-Based Approach to Lung Disease What is your favored diagnosis? 1. Usual interstitial pneumonia (UIP) 2. Nonspecific interstitial pneumonia (NSIP) 3. Mixed dust pneumoconiosis 4. Langerhans cell histiocytosis 5. Desquamative interstitial pneumonia (DIP)

A Pattern-Based Approach to Lung Disease Clinical history A 44-year-old woman developed progressive shortness of breath accompanied by pulmonary infiltrates and non-productive cough. Chest imaging reveals mid and upper lung zone, ill-defined, 2-3 mm nodules in the lung periphery.

A Pattern-Based Approach to Lung Disease What is the pattern? 1. Acute injury 2. Fibrosis 3. Cellular 0 infiltrates 4. Alveolar filling 5. Nodules 6. Minimal changes

A Pattern-Based Approach to Lung Disease What is your favored diagnosis? 1. Hypersensitivity pneumonitis 2. Nonspecific interstitial pneumonia (NSIP) 3. MALT lymphoma 4. Lymphoid Interstitial Pneumonia (LIP) 5. Usual interstitial pneumonia (UIP)

A Pattern-Based Approach to Lung Disease Clinical history A 47-year-old woman presents with unexplained persistent cough over several months. Constitutional symptoms are mild, with minimal shortness of breath on exertion. Chest imaging shows sharply defined areas of ground-glass attenuation alternating with normal appearing lung.

A Pattern-Based Approach to Lung Disease What is your favored diagnosis? 1. Pulmonary edema 2. Pneumocystis pneumonia 3. Alveolar proteinosis 4. Pneumoconiosis (Aluminosis) 5. Drug toxicity

A Pattern-Based Approach to Lung Disease Kevin O. Leslie. MD Case 5

A Pattern-Based Approach to Lung Disease Clinical history A 36-year-old woman presents for follow-up screening one year after being diagnosed and treated for invasive ductal adenocarcinoma of the right breast. Imaging reveals miliary bilateral nodules involving the mid and upper lung zones.

A Pattern-Based Approach to Lung Disease What is your favored diagnosis 1. Metastatic carcinoma 2. Mixed dust pneumoconiosis 3. Langerhans cell histiocytosis 4. Sarcoidosis 5. Capillary hemangiomatosis

A Pattern-Based Approach to Lung Disease Clinical history A 33-year-old woman presents with unexplained progressive shortness of breath accompanied by non-productive cough. She is significantly hypoxic on room air and pulmonary function testing reveals obstructive physiology. CT imaging is interpreted as showing patchy ground glass opacities, which appeared to be enhanced in expiratory views.

Expiratory HRCT

A Pattern-Based Approach to Lung Disease What is your favored diagnosis? 1. Pulmonary hypertension 2. Chronic small airways disease 3. Lymphangitic carcinoma 4. Lymphangioleiomyomatosis (LAM) 5. Sampling error

Constrictive bronchiolitis Airway!

1 Fortune favors the prepared mind! --Louis Pasteur 2 6

Take home lessons Surgical Pathology has evolved to medical pathology in many specialty areas. This requires the addition of clinical and imaging skills. Using a pattern-based approach with clinical, radiologic, and histopathologic patterns enhances dramatically the relevant interpretation of lung biopsies.

Thank You! Questions