Xi CONTENTS 1. Embryology and Anatomy

CONTENTS

1. Embryology and Anatomy...... 1 Embryology ...... 1 Anatomy and Histology...... 5 2. Handling and Analysis of Bronchoalveolar Lavage and Lung Biopsy Specimens with Approach to Patterns of Lung Injury...... 17 Clinical and Radiologic Correlation...... 17 Bronchoalveolar Lavage...... 18 Handling and Processing of Specimens...... 20 Types of Lung Biopsy Specimens...... 20 Transbronchial Biopsies...... 21 Surgical Lung Biopsies...... 22 Special Stains...... 23 Special Techniques...... 23 Electron Microscopy ...... 24 General Principles in Lung Biopsy Interpretation...... 24 Patterns of Lung Injury ...... 32 Anatomic Distribution...... 34 Reaction Patterns...... 35 Practical Aspects...... 37 3. Idiopathic Interstitial Pneumonia and Other Diffuse Parenchymal Lung Diseases . . . . 49 General Approach to Diffuse Parenchymal Lung Diseases...... 49 The Initial Evaluation of Patients with Suspected DPLD...... 49 Clinical Features...... 49 Signs and Symptoms ...... 51 Laboratory Tests...... 51 Bronchoalveolar Lavage and Lung Biopsy...... 52 Classification of Idiopathic Interstitial Pneumonias...... 53 Liebow Classification...... 53 Katzenstein and Müller/Colby Classifications...... 53 American Thoracic Society/European Respiratory Society Classification...... 54 Commonly Encountered Problems in the Clinical and Pathologic Classification of the Idiopathic Interstitial Pneumonias...... 55 Differential Diagnosis of Interstitial Pneumonias...... 58 Usual Interstitial Pneumonia (Idiopathic Pulmonary Fibrosis/Cryptogenic Fibrosing Alveolitis)...... 59

xi Non-Neoplastic Disorders of the Lower Respiratory Tract

Nonspecific Interstitial Pneumonia, Cellular and Fibrosing Patterns...... 73 Evolving Concept of NSIP...... 82 Cryptogenic Organizing Pneumonia (Bronchiolitis Obliterans Organizing Pneumonia)...... 82 Diffuse Alveolar Damage and Acute Interstitial Pneumonia...... 89 Acute Fibrinous and Organizing Pneumonia ...... 101 Acute Interstitial Pneumonia (Idiopathic Diffuse Alveolar Damage)...... 103 Respiratory Bronchiolitis–Interstitial Lung Disease...... 106 Desquamative Interstitial Pneumonia...... 109 Hypersensitivity Pneumonitis...... 115 Sarcoidosis ...... 123 Langerhans’ Cell Histiocytosis and Other Histiocytic Disorders...... 136 Langerhans’ Cell Histiocytosis...... 136 Erdheim-Chester Disease...... 144 Sinus Histiocytosis with Massive Lymphadenopathy...... 144 Lymphangioleiomyomatosis...... 147 Eosinophilic Pneumonia ...... 160 Idiopathic Eosinophilic Pneumonias...... 162 Simple Eosinophilic Pneumonia...... 162 Chronic Eosinophilic Pneumonia...... 162 Acute Eosinophilic Pneumonia...... 164 Secondary Eosinophilic Pneumonias...... 167 Infectious Eosinophilic Pneumonia...... 168 Drug-Induced Eosinophilic Pneumonia ...... 168 Immunologic or Systemic Diseases...... 168 Differential Diagnosis of Eosinophilic Pneumonia...... 168 Treatment and Prognosis...... 169 Pulmonary Alveolar Proteinosis...... 169 Diffuse Alveolar Hemorrhage...... 176 Antibasement Membrane Antibody Disease (Goodpasture’s Syndrome)...... 184 Idiopathic Pulmonary Hemorrhage...... 185 Aspiration...... 187 Alveolar Microlithiasis...... 196 4. Pulmonary Vasculitis ...... 233 Wegner’s Granulomatosis...... 234 Churg-Strauss Syndrome ...... 244 Microscopic Polyangiitis...... 248 Necrotizing Sarcoid Granulomatosis...... 251 Other Rare Causes of Granulomatous Arteritis...... 254

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Giant Cell Arteritis...... 254 Disseminated Visceral Giant Cell Angiitis...... 254 Polyarteritis Nodosa...... 255 Takayasu’s Arteritis...... 255 Behçet’s Syndrome...... 255 Secondary Vasculitis...... 258 Pulmonary Infection and Septic Emboli...... 258 Classic Sarcoidosis...... 258 5. Reactive Lymphoid Lesions ...... 265 Introduction...... 265 Lymphocytic Interstitial Pneumonia...... 266 Follicular Bronchitis/Bronchiolitis...... 276 Nodular Lymphoid Hyperplasia of Lung...... 277 Giant Lymph Node Hyperplasia (Castleman’s Disease)...... 282 Intrapulmonary Lymph Nodes ...... 283 6. Connective Tissue and Inflammatory Bowel Diseases...... 291 Histologic Spectrum of the Pleuroparenchymal Reactions...... 291 Rheumatoid Arthritis...... 293 Systemic Lupus Erythematosus ...... 300 Scleroderma ...... 302 Polymyositis/Dermatomyositis ...... 304 Sjögren’s Syndrome ...... 307 Mixed Connective Tissue Disease ...... 308 Ankylosing Spondylitis...... 309 Relapsing Polychondritis...... 310 Inflammatory Bowel Disease...... 310 7. Drug and Radiation Reactions ...... 321 Drug Reactions...... 321 Definition and Background...... 321 Clinical Syndromes Associated with Pulmonary Drug Reactions...... 324 Pathologic Patterns Associated with Pulmonary Drug Reactions...... 326 Diagnosing and Treating Pulmonary Drug Reactions...... 340 Radiation Lung Injury ...... 340 8. Bronchiolar Disorders...... 351 Introduction...... 351 Background...... 351 Pathologic Patterns of Bronchiolitis...... 353 Clinical Manifestations ...... 362

xiii Non-Neoplastic Disorders of the Lower Respiratory Tract

Radiologic Manifestations ...... 362 Clinicopathologic Entities...... 368 Asthma...... 368 Infectious Bronchiolitis and Postinfectious Constrictive Bronchiolitis ...... 368 Fume-Related Bronchiolar Injury ...... 370 Diffuse Panbronchiolitis ...... 373 Idiopathic Bronchiolitis (Including Cryptogenic Obliterative Bronchiolitis). . . . . 375 9. Bronchial Disorders...... 381 Introduction ...... 381 Infectious Bronchitis...... 382 Bronchiectasis...... 382 Cystic Fibrosis...... 392 Primary Ciliary Dyskinesia...... 399 Middle Lobe Syndrome...... 404 Bronchocentric Granulomatosis...... 408 Mucoid Impaction of Bronchi...... 412 Allergic Bronchopulmonary Fungal Disease...... 415 Plastic Bronchitis...... 419 Relapsing Polychondritis...... 421 Tracheobronchomegaly...... 423 Congenital Bronchial Cartilage Deficiency...... 424 Broncholithiasis...... 426 10. Obstructive Pulmonary Diseases...... 435 Chronic Bronchitis ...... 435 Emphysema...... 441 Pathologic Evaluation of the Lung for Emphysema...... 443 Proximal Acinar Emphysema (Centriacinar or Centrilobular Emphysema) . . . . . 443 Panacinar Emphysema...... 449 Distal Acinar Emphysema...... 452 Irregular Emphysema ...... 454 Localized Giant Bullous Emphysema...... 455 Simple (Nonemphysematous) Airspace Enlargement...... 456 Asthma ...... 457 11. Congenital Anomalies and Pediatric Disorders...... 473 Introduction ...... 473 Anomalies of the Tracheobronchial Tree ...... 474 Bronchogenic Cyst ...... 478 Pulmonary Sequestration ...... 481

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Intralobar Sequestrations ...... 481 Extralobar Sequestrations...... 484 Anomalies of the Lung Parenchyma...... 486 Congenital Cystic Adenomatoid Malformation...... 489 Infantile Lobar Emphysema/Polyalveolar Lobe...... 496 Vascular Anomalies...... 497 Ectopic Tissues in the Lung...... 507 Respiratory Distress Syndrome of the Newborn...... 507 Bronchopulmonary Dysplasia...... 511 Pulmonary Interstitial Emphysema ...... 518 Meconium Aspiration Syndrome ...... 522 Massive Pulmonary Hemorrhage of the Newborn...... 525 Pediatric Interstitial Lung Disease...... 525 12. Lung Infections...... 539 Bacterial Pneumonias ...... 539 Common Bacterial Pneumonias...... 541 Streptococcus Pneumoniae ...... 541 Staphylococcus Sp...... 544 Streptococcus Sp (Nonpneumococcal) ...... 547 Haemophilus Influenzae ...... 548 Klebsiella Pneumoniae...... 549 Pseudomonas Aeruginosa...... 550 Legionella Sp...... 553 Anaerobic Bacteria...... 556 Nocardia Sp ...... 557 Actinomyces Sp...... 560 Uncommon Bacterial Pneumonias...... 563 Burkholderia Pseudomallei...... 563 Francisella Tularensis ...... 565 Yersinia Pestis...... 566 Rhodococcus Equi and Malakoplakia ...... 569 Botryomycosis...... 571 Bacillary Angiomatosis...... 574 Tropheryma Whippelii (Whipple’s Disease) ...... 575 Lung Abscess...... 576 Mycobacterial Pneumonias...... 579 Mycobacterium Tuberculosis ...... 579 Nontuberculous Mycobacteria...... 587

xv Non-Neoplastic Disorders of the Lower Respiratory Tract

Fungal Infections...... 592 Histoplasma Capsulatum ...... 592 Cryptococcus Sp ...... 600 Coccidioides Immitis...... 605 Blastomyces Dermatitides ...... 611 Paracoccidioides Brasiliensis ...... 614 Aspergillus Sp...... 616 Zygomycetes...... 627 Candida Sp...... 629 Sporothrix Schenkii ...... 632 Fusarium Sp...... 635 Pseudoallescheria Boydii ...... 635 Chrysosporium Parvum...... 636 Malassezia Furfur...... 636 Viral Infections ...... 638 Cytomegalovirus...... 639 Herpes Simplex...... 642 Varicella-Zoster...... 646 Adenovirus ...... 648 Respiratory Syncytial Virus...... 651 Measles ...... 653 Parainfluenza...... 656 Influenza...... 657 Hantavirus...... 660 Mycoplasmal and Chlamydial Pneumonias...... 661 Mycoplasma Pneumoniae ...... 662 Chlamydia Sp...... 665 Pneumocystis Carinii Pneumonia...... 668 Parasitic Infections ...... 680 Protozoa...... 680 Toxoplasmosis...... 680 Amebiasis...... 683 Cryptosporidiosis ...... 684 Microsporidiosis ...... 687 Nematoda ...... 689 Dirofilariasis ...... 689 Filariasis...... 691 Strongyloidiasis...... 692

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Trematoda...... 694 Paragonimiasis...... 694 Schistosomiasis...... 696 Cestoda ...... 699 Echinococcosis ...... 699 Pseudoparasitic Structures...... 704 13. Interpretation of Lung Biopsies from Immunocompromised Patients and Patients with Acquired Immunodeficiency Syndrome...... 729 Diagnosis of Pulmonary Complications in Immunocompromised Patients...... 729 Lung Biopsy Interpretation in Immunocompromised Patients...... 730 Radiologic Patterns in Immunocompromised Patients ...... 730 Pathologic Patterns in Lung Biopsies from Immunocompromised Patients...... 732 Pulmonary Complications of HIV Infection and AIDS ...... 734 Noninfectious Pulmonary Complications of HIV Infection ...... 736 Pulmonary Lymphoid Lesions ...... 736 Chronic Interstitial Pneumonia Associated with Nonspecific Interstitial Pneumonia ...... 736 Pathogenesis of Lymphoid Lesions in HIV-Infected Patients...... 738 Lymphocytic Alveolitis...... 739 Diffuse Infiltrative Lymphocytosis Syndrome ...... 740 Diffuse Alveolar Damage...... 740 Organizing Pneumonia (Cryptogenic Organizing Pneumonia/Bronchiolitis Obliterans Organizing Pneumonia)...... 740 Obstructive Lung Disease and Bronchiectasis ...... 741 Eosinophilic Pneumonia...... 741 Sarcoidosis...... 742 Alveolar Proteinosis...... 742 Pulmonary Hypertension...... 742 14. Transplantation Pathology ...... 747 General Principles in Diagnosis of Pulmonary Complications in Transplant Recipients ...... 747 Diagnosis of Pulmonary Complications...... 747 Evaluation of Transbronchial Lung Biopsies ...... 747 Early Complications ...... 749 Reperfusion Injury...... 749 Acute Cellular Rejection...... 751 Diffuse Alveolar Hemorrhage...... 754 Late Complications...... 755 Obliterative (Constrictive) Bronchiolitis ...... 755

xvii Non-Neoplastic Disorders of the Lower Respiratory Tract

Post-Transplant Lymphoproliferative Disorders...... 760 15. Pulmonary Hypertension and Other Vascular Disorders...... 767 Normal Pulmonary Circulation ...... 767 World Health Organization Classification of Pulmonary Hypertension...... 768 Role of Histologic Assessment in the Diagnosis of Pulmonary Vascular Diseases. 769 Pulmonary Arterial Hypertension...... 769 Pulmonary Venous Hypertension...... 777 Pulmonary Veno-Occlusive Disease ...... 779 Pulmonary Hypertension Associated with Disorders of the Respiratory System and/or Hypoxemia...... 781 Pulmonary Hypertension Due to Chronic Thrombotic and/or Embolic Disease . . . 782 Pulmonary Hypertension Due to Disorders Directly Affecting the Pulmonary Vasculature ...... 787 Pulmonary Capillary Hemangiomatosis...... 788 16. Occupational Lung Diseases and Pneumoconioses ...... 793 Introduction and General Principles ...... 793 Coal Worker’s Pneumoconiosis...... 795 Pneumoconiosis from Other Carbonaceous Materials...... 802 Silicosis ...... 803 Asbestosis and Other Non-Neoplastic Diseases Caused by Asbestos ...... 814 Background, Mineralogy, and Exposure...... 814 Asbestosis...... 815 Asbestos Airway Disease...... 822 Benign Asbestos Pleural Effusion (Benign Asbestos Pleurisy)...... 823 Visceral Pleural Fibrosis...... 825 Hyaline Parietal Pleural Plaques...... 826 Rounded Atelectasis ...... 827 Overlap Among Non-Neoplastic Asbestos-Related Diseases of the Lung and Pleura...... 829 Silicatoses...... 829 Pulmonary Siderosis ...... 833 Mixed Dust Reactions...... 834 Berylliosis...... 835 Hard Metal (Cobalt) Lung Disease ...... 840 Pulmonary Disease and Exposure to Other Metals...... 842 Pulmonary Disease Associated with Inhalation of Gases and Fumes...... 844 Effects of Inhalation of Synthetic Fibers on the Lung ...... 845 Nylon Flock Worker’s Lung...... 845 Occupational Asthma and Reactive Airways Dysfunction Syndrome...... 846

xviii Contents

Occupational Extrinsic Allergic Alveolitis...... 847 Byssinosis...... 847 Organic Dust Toxic Syndrome ...... 848 Pulmonary Disease Associated with Intravenous Drug Exposure ...... 849 17. Miscellaneous Diseases of Uncertain Etiology ...... 857 Introduction ...... 857 Inflammatory Pseudotumor (Inflammatory Myofibroblastic Tumor)...... 857 Pulmonary Hyalinizing Granuloma...... 867 Pulmonary Amyloidosis ...... 872 Metastatic Calcification...... 881 Dystrophic Pulmonary Ossification ...... 885 Tracheobronchopathia Osteochondroplastica...... 888 Endometriosis...... 888 Bronchial Inflammatory Polyps ...... 890 Pulmonary Involvement in Inborn Errors of Metabolism...... 890 Gaucher’s Disease ...... 891 Niemann-Pick Disease...... 892 Fabry’s Disease (Angiokeratoma Corporus Diffusinum Universali)...... 892 Hermansky-Pudlak Syndrome...... 892 Marfan’s Syndrome...... 893 Ehlers-Danlos Syndrome...... 893 Miscellaneous Diseases...... 893 18. Pleural Disorders...... 901 Pneumothorax...... 901 Pleural Effusion...... 905 Pleuritis...... 910 Index...... 923

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