Dail and Hammar's Pulmonary Pathology (eBook)

Preface 6
Table of Contents 9
Contributors 12
32 Lymphoproliferative Diseases 16
Normal Lymphoid Tissue and Lymphatic Routes of the Lung 16
Lymphoid Hyperplasias, Benign Lymphoid Infifiltrates, and Related Lesions 18
Lymphocytic Interstitial Pneumonia 20
Pseudolymphoma or Nodular Lymphoid Hyperplasia 22
Malignant Lymphomas Presenting in the Lung 23
Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue 25
Lymphomatoid Granulomatosis 31
Posttransplant Lymphoproliferative Disorders 36
Lymphoproliferative Disorders in the Setting of Human Immunodefificiency Virus Infection and Acquired Immune Defificiency Syndrome 37
Primary Effusion Lymphoma 38
Lymphoproliferative Disorders Associated with Primary Immunodefificiency States 39
Hodgkin’s Lymphoma Presenting in the Lung 39
Anaplastic Large Cell Lymphoma Presenting in the Lung 42
Other Lymphomas Presenting in the Lung 43
Lymphomas with Secondary Lung Involvement 45
Mature B-Cell Lymphoproliferative Disorders 45
B-cell Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia 45
Mantle Cell Lymphoma 45
Follicular Lymphoma 46
Mature T-Cell Lymphoproliferative Disorders 47
Histiocytic Disorders 47
Erdheim-Chester Disease 48
Rosai-Dorfman Disease 49
Leukemic Infifiltrates in the Lung 49
Plasma Cell Tumors and Multiple Myeloma 52
Pleural Lymphoma and Leukemia 52
Miscellaneous Hematolymphoid Disorders 52
Systemic Mast Cell Disease 52
Immune Accessory Cell Neoplasms 53
Follicular Dendritic Cell Tumors 53
33 Molecular Genetics of Lung and Pleural Neoplasms 62
Basic Concepts and Terminology 62
Nucleic Acids, Genes, and Gene Products 62
Posttranslational Modififications of Gene Products and Protein Degradation 64
Phosphorylation and Acetylation 64
Protein Degradation and Ubiquitinylation 64
Transcription Factors 64
Cell Surface Receptors and Signal Transduction 65
Ras/Raf-1/Mitogen-Activated Protein Kinase Pathway 66
JAK Family 66
Transforming Growth Factor-ß Superfamily 66
Wnt/B-Catenin Pathway 66
PI3K/Akt/mTOR Pathway 67
Hedgehog-Patched-Smoothened Signaling Pathway 67
Notch 67
DNA Damage Repair 67
The Cell Cycle 68
Cell Death and Survival 70
Apoptosis 70
Survival Pathways 71
Mutations 72
MicroRNAs and siRNAs 73
Molecular Procedures 73
General Principles and Techniques 73
Specifific Procedures 74
Southern Blot 74
Dot Blots and Slot Blots 75
Northern Blots and Western Blots 75
Polymerase Chain Reaction 75
Denaturing Gradient Gel Electrophoresis and Temperature Gradient Gel Electrophoresis 77
Heteroduplex Analysis 77
Single-Strand Conformation Polymorphism 77
Bioinformatics and Omics 77
DNA Microarrays, DNA Chips, and Gene Expression Chips 78
Suppression Subtractive Hybridization 78
Serial Analysis of Gene Expression 78
Two-Dimensional Gel Electrophoresis and Mass Spectrometry 79
Tissue Microarrays 79
Molecular Cytogenetics 79
Fluorescence In-Situ Hybridization 79
Chromogenic In-Situ Hybridization 79
Comparative Genomic Hybridization 80
Genetic Susceptibility to Lung Cancer 80
Risk of Developing Lung Cancer 80
Familial Risk of Lung Cancer 80
Gender and Risk of Lung Cancer 80
Xenobiotic-Metabolizing Enzymes 81
DNA Adducts and Lung Cancer 82
Polymorphisms and Adduct Levels 82
Investigations of Specifific Polymorphisms and Lung Cancer Susceptibility 83
Xenobiotic Metabolizing Genes 83
CYP Polymorphisms and Susceptibility to Lung Cancer 83
CYP2A6 84
Other CYP Alleles 84
Aryl Hydrocarbon Receptor 84
Microsomal Epoxide Hydrolase 84
Glutathione-S-Transferases and Susceptibility to Lung Cancer 84
Other Phase II Xenobiotic Enzymes 84
Multiple Xenobiotic Metabolizing Enzymes 84
DNA Repair Gene Polymorphisms and Susceptibility to Lung Cancer 85
Nucleotide Excision Repair Pathway Polymorphisms 85
Other DNA Repair Genes 86
Multiple DNA Repair Genes 86
Other Markers of Lung Cancer Susceptibility 86
Molecular Pathology of Lung Cancer 86
Carcinogenesis 86
Pulmonary Carcinogens and Their Impact on Genes 87
Field Cancerization 88
Prevention of Damage and Repair Mechanisms 88
Nuclear Structure in Cancer Cells 89
Chromosomal Abnormalities Found in Carcinoma Cells 89
Small Cell Lung Carcinoma 89
Adenocarcinoma 92
Squamous Cell Carcinoma 93
Large Cell Carcinoma 95
Molecular Biomarkers of Lung Cancer Prognosis 96
Molecular Pathology and Therapy 97
Response to Conventional Therapies (Customized Therapy) 97
Thioredoxin-1 97
Excision Repair Cross-Complementing Group I (ERCC1) 97
BRCA1 98
14-3-3 Proteins 98
Targeted Therapies 98
Epidermal Growth Factor Receptor Targeted Therapies 98
C-Kit Antagonist Imatinib Mesylate 98
ErbB2/HER2/Herceptin (Trastuzumab) and ERbB2/HER2/Pertuzumab 98
Antiangiogenesis Therapy 99
Farnesyl Transferase Inhibitors 99
Epigenetic Therapy General 99
Molecular Pathology of Other Lung Tumors 100
Uncommon Carcinomas of the Lung 100
Pleomorphic Carcinomas (See Also Chapter 37) 100
Carcinoids (See Also Chapter 36) 100
Benign Lung Tumors 100
Papilloma (See Also Chapters 7, 34, and 35) 100
Hamartoma (See Also Chapter 40) 101
Solitary Fibrous Tumor (See Also Chapters 39 and 43) 101
Mixed Epithelial/Mesenchymal Cancers and Sarcomas of the Lung 101
Pulmonary Blastoma (See Also Chapters 37 and 42) 101
Synovial Sarcoma, Leiomyosarcoma, Malignant Fibrous Histiocytoma, and Malignant Peripheral Nerve Sheath Tumor (See Also Chapters 39 to 41) 102
Diffuse Malignant Mesothelioma (See Also Chapter 43) 103
References 103
34 Preinvasive Disease 173
Preexisting Lung Disease and Lung Cancer 173
Localized Lung Fibrosis: The “Scar Cancer” Hypothesis 173
Diffuse Lung Fibrosis and Lung Cancer 174
Idiopathic Pulmonary Fibrosis 175
Connective Tissue Disease 176
Mineral Pneumoconiosis 177
Other Lung Lesions and Lung Cancer 177
Cystic Adenomatoid Malformation 177
Juvenile Tracheobronchial Squamous Papillomatosis 178
Cysts, Sequestration, and Bronchiectasis 178
Preinvasive Lesions in the World Health Organization Classifification 178
Squamous Dysplasia/Carcinoma-in-Situ and Other Bronchial Preinvasive Lesions 179
Basal Cell Hyperplasia 179
Goblet Cell Hyperplasia 179
Squamous Metaplasia 180
Sqaumous Dysplasia and Carcinoma-in-Situ 180
Historical Perspective 184
Issues in the Diagnosis of Preinvasive Bronchial Lesions 186
Progression of Squamous Dysplasia/Carcinoma in Situ to Invasive Disease 188
Cell and Molecular Biology of Squamous Dysplasia/Carcinoma in Situ 189
Atypical Adenomatous Hyperplasia 197
Morphology of Atypical Adenomatous Hyperplasia 198
Associations and Prevalence of Atypical Adenomatous Hyperplasia 202
Evidence in Support of Atypical Adenomatous Hyperplasia as a Preinvasive Lesion: Morphology, Morphometry, and Cytoflfluorimetry 204
Evidence in Support of Atypical Adenomatous Hyperplasia as a Preinvasive Lesion: Cell and Molecular Biology 205
Atypical Adenomatous Hyperplasia: Possible Etiologic Factors 209
Atypical Adenomatous Hyperplasia: Risk of Progression and Prognostic Implication 210
Peripheral Lung Adenocarcinogenesis: An Adenoma-Carcinoma Sequence 210
Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia 212
Morphology 212
Pulmonary Neuroendocrine Cell Hyperplasia Without DIPNECH 212
Origin of High-Grade Neuroendocrine Tumors 215
Lung Tumor Development: Lessons from Immunocytochemistry and Genetics 216
Preinvasive Lung Lesions: Lessons for and from Lung Cancer Screening 216
Conclusion 218
References 219
35 Common Non–Small-Cell Carcinomas and Their Variants 231
Epidemiology 231
Incidence and Mortality 231
Gender 231
Age 233
Race 234
Histology 234
Etiology 235
Tobacco 235
Environmental Factors 238
Occupational Factors 240
Infections 242
Lung Injury 243
Diet 244
Familial and Genetic Factors 245
Lung Cancer Screening 246
Clinical Manifestations 248
Methods of Diagnosis 250
Staging 251
Histogenesis of Common Lung Neoplasms 254
Histologic Classifification of Lung Cancer 256
Squamous Cell Carcinoma 258
Squamous Cell Carcinoma Variants 263
Papillary Variant 263
Clear Cell Variant 264
Small Cell Variant 264
Basaloid Variant 264
Adenocarcinoma 265
Nonbronchioloalveolar Carcinoma 267
Bronchioloalveolar Carcinoma 273
Adenocarcinoma Variants 280
Large Cell Carcinoma 288
Large Cell Carcinoma Variants 290
Adenosquamous Carcinoma 293
Conclusion 295
References 295
36 Neuroendocrine Tumors 323
Neuroendocrine Neoplasms of the Lung 323
Identifification of Neuroendocrine Cells and Neuroendocrine Neoplasms 323
Histochemical Identififi cation 323
Neuroendocrine Cells 323
Immunohistochemical-Biochemical Identifification 324
Chromogranins 324
Neurofifilaments 325
Synaptophysin 325
Leu7 325
Monoclonal Antibody 735 325
Thyroid Transcription Factor 1 325
CD117 325
Other Immunocytochemical Markers 326
Ultrastructural Identifification 326
Molecular Biology Techniques 326
Normal Neuroendocrine Cells of the Lung 326
Nomenclature of Neuroendocrine Neoplasms of Lung 328
Preinvasive Lesions 329
Neuroendocrine Neoplasms 329
Tumorlet 329
Typical Carcinoid 330
Atypical Carcinoid 336
Large Cell Neuroendocrine Carcinoma 338
Small Cell Lung Carcinoma 342
Combined Small Cell-Large Cell Neuroendocrine Carcinomas 349
Combined Small Cell–Non–Small-Cell Lung Neoplasms 351
Unusual Neuroendocrine Lung Neoplasms 353
Case 1 (Anemone Tumor) 353
Case 2 (Primitive Neuroectodermal Tumor) 353
Case 3 (Pulmonary Blastoma with Neuroendocrine Differentiation) 355
Case 4 (Neuroendocrine Carcinoma) 356
Case 5 (Amphicrine Carcinoma) 357
Neuroendocrine Differentiation in Non–Small-Cell Lung Carcinomas 358
Immunohistochemical Features of Neuroendocrine Lung Cancers 360
Genetic Studies (See Also Chapter 33) 363
Approach to the Diagnosis of Neuroendocrine Lung Neoplasms: Variabilities and Pitfalls 364
Differential Diagnosis 366
Lymphoma 366
Small Cell Squamous Carcinoma 367
Small Cell Adenocarcinoma 368
Basaloid Carcinoma 368
Pleural Neoplasms 368
Metastatic Carcinoma 368
Clinicopathologic Correlations 370
Prognosis 370
Typical and Atypical Carcinoids 370
Small Cell Carcinoma Versus Atypical Carcinoid 375
Large Cell Neuroendocrine Carcinomas 376
Small Cell Carcinoma 377
Other General Studies of Neuroendocrine Carcinomas 380
Conclusion 382
References 382
37 Sarcomatoid Carcinoma: Pleomorphic Carcinoma, Spindle Cell Carcinoma, Giant Cell Carcinoma, Carcinosarcoma, and Pulmonary Blastoma 390
Defifinition 390
Sarcomatoid Carcinoma (Pleomorphic Carcinoma, Spindle Cell Carcinoma) 390
Clinical and Radiologic Features 391
Pathology 391
Macroscopic Appearance 391
Histopathology 391
Immunohistochemistry 393
Electron Microscopy 395
Genetic Studies in Pleomorphic Carcinoma 395
Metastatic Sites 396
Prognostic Factors and Survival 396
Giant Cell Carcinoma 396
Epidemiology 396
Clinical and Radiologic Findings 396
Pathology 397
Macroscopic Appearance 397
Histopathology 397
Immunohistochemistry 397
Electron Microscopy 398
Genetic Studies in Giant Cell Carcinoma 398
Metastatic Sites 398
Prognosis 398
Carcinosarcoma 398
Epidemiology 398
Clinical and Radiologic Findings 398
Pathology 399
Macroscopic Appearance 399
Histopathology 399
Immunohistochemistry 400
Genetic Studies 400
Metastatic Sites 400
Prognosis 400
Pulmonary Blastoma 400
Clinical and Radiologic Features 401
Pathology 401
Macroscopic Appearance 401
Histopathology 402
Cytology 402
Immunohistochemistry 403
Electron Microscopy 403
Genetic Studies 404
Metastases 405
Prognosis 405
Differential Diagnosis of Sarcomatoid Carcinoma 405
Pleomorphic Carcinoma 405
Inflammatory Myofifibroblastic Tumor 405
Idiopathic Fibroinflammatory (Fibrosing/Sclerosing) Mediastinal Lesions 405
Primary Pulmonary Malignant Fibrous Histiocytoma 406
Malignant Endobronchial Myxoid Tumor 406
Secondary Carcinoma 406
Non–Small-Cell Carcinoma 406
Thymic Tumors 406
Pulmonary Neuroendocrine Tumors 406
Mesothelioma and Other Pleural Tumors 406
Sarcomas 407
Small Cell Carcinoma 407
Rhabdoid Features Associated with Large Cell Carcinoma of Lung 407
Germ Cell Tumor and Teratoma 407
Carcinosarcoma 407
Pulmonary Blastoma 407
Pleuropulmonary Blastoma 407
Well-Differentiated Fetal Adenocarcinoma 407
Teratoma 407
Hamartoma 407
Myxoid Liposarcoma 407
Myxoma of the Pleura 407
Histogenesis 407
Conclusion 408
References 408
38 Tracheobronchial Tumors of the Salivary Gland Type 413
Pleomorphic Adenoma 413
Mucoepidermoid Tumors 415
Adenoid Cystic Carcinomas 419
Mucous Gland Adenomas 423
Acinic Cell Tumors 424
Pulmonary Oncocytic Change and Oncocytomas 426
Myoepithelioma and Epithelial-Myoepithelial Tumors 428
Low-Grade Adenocarcinomas with Polymorphous Features 431
Other Tumors Believed to Be of Salivary Gland Origin 432
References 437
39 Mesenchymal Tumors, Part I: Tumors of Fibrous, Fibrohistiocytic, and Muscle Origin 442
Tumors of Fibrous and Fibrohistiocytic Origin 442
Inflammatory Pseudotumor (Inflammatory Myofibroblastic Tumor) 442
Intrapulmonary Localized Fibrous Tumor 444
Cystic Fibrohistiocytic Tumors 445
Mesenchymal Cystic Hamartoma 448
Fibrous Histiocytoma 449
Malignant Fibrous Histiocytoma (Undifferentiated Sarcoma) 450
Fibrosarcoma 452
Tumors of Muscle Origin 452
Nodular Smooth Muscle Proliferation and Leiomyoma 452
Benign Metastasizing Leiomyoma 454
Leiomyosarcoma 457
Lymphangioleiomyomatosis 458
Glomus Tumor 467
Rhabdomyoma, Rhabdomyomatous Dysplasia, and Rhabdomyosarcoma 469
References 471
40 Mesenchymal Tumors, Part II: Tumors of Hamartomatous, Osteochondromatous, Lipomatous, Neural, and Vascular Origin 477
Pulmonary Hamartomas 477
Pulmonary Chondroma 481
Chondrosarcoma 482
Osteosarcoma 483
Lipoma and Liposarcoma 484
Neurogenic Tumors 486
Malignant Mesenchymoma 488
Hemangioma 488
Hemangiomatosi 490
Arteriovenous Malformations 491
Lymphangiectasia, Lymphangiomas, and Lymphangiomatosis 492
Hemangiopericytomas (Localized Fibrous Tumors) 495
Epithelioid Hemangioendotheliomas 496
Angiosarcoma 501
Pulmonary Artery Sarcomas 503
Kaposi’s Sarcoma 505
References 509
41 Miscellaneous Tumors and Tumor-Like Proliferations of the Lung 515
Tissue Ectopias and Primary Pulmonary Tumors Derived from Ectopic Tissues 515
Pulmonary Endometriosis 515
Pulmonary Thymomas 518
Primary Malignant Melanomas 520
Pulmonary Meningothelial-Like Bodies 523
Meningiomas 526
Ependymomas 529
Germ Cell Tumors 529
Synovial Sarcomas 531
Sclerosing Hemangiomas 532
Alveolar and Papillary Adenomas 537
Inflammatory Bronchial Polyps 541
Benign Clear Cell (Sugar) Tumor 541
Granular Cell Tumor 545
Paraganglioma 547
Uncommon Endobronchial Surface Tumors 549
Squamous Papillomas 549
Glandular Papillomas 550
Mixed squamous and glandular papillomas 551
References 551
42 Pediatric Tumors 557
Inflammatory Myofibroblastic Tumor 557
Peribronchial Myofibroblastic and Smooth Muscle Tumors 559
Cartilaginous Lesions 560
Vascular Neoplasms and Malformations 561
Pulmonary Blastoma 561
Pleuropulmonary Blastoma 562
Other Sarcomas 565
Epithelial Tumors 566
Langerhans Cell Histiocytosis and Lymphoid Neoplasms 568
Metastatic Tumor 569
References 569
43 Neoplasms of the Pleura 573
Pleural Neoplasms 573
Mesothelioma 573
Definitions, History, Incidence, and Epidemiology 573
Definition 573
History 573
Incidence and Epidemiology 574
Etiology 576
Asbestos 576
Proposed Nonasbestos Causes of Mesothelioma 578
Occupations at Risk 583
Pleural/Peritoneal Mesothelioma Ratios 585
Latency Intervals Between the Commencement of Asbestos Exposure and the Subsequent Diagnosis of Mesothelioma 588
Mineral Fibers and Mesothelioma 588
Fiber Length and Mesothelioma 588
Nonasbestos and Nonoccupational Mineral Fibers and Mesothelioma 589
Identification of Tissue Markers of Past Exposure (Ferruginous Bodies and Uncoated Fibers) 589
Studies Defining Mineral Fiber Content in Mesothelioma Patients 590
Asbestos Fiber Types and Dose, and Mesothelioma Risk and Induction 594
Is a Threshold or Minimal Level of Asbestos Exposure/Inhalation Required for Mesothelioma Induction? 596
Commercial Chrysotile and Mesothelioma: Can Chrysotile-Only Exposure Induce Mesothelioma? 597
The Quebec Chrysotile Cohort 598
Other Chrysotile-Exposed Cohorts and Studies 598
Chrysotile Content of Human Lung Tissue from Mesothelioma Patients 599
Chrysotile-Only Exposure: Asbestos and Mesothelioma Among Automotive and Brake Mechanics 600
Summary 602
The Molecular Pathogenesis and Pathology of Malignant Mesothelioma 602
Molecular Events in the Development of Mesothelioma I: Physical Interaction Between Fibers and Cells 603
Molecular Events in the Development of Mesothelioma II: Free Radicals 603
Indirect Toxic Effects 603
Interference with Apoptosis 604
Direct Activation of Transcription Pathways 605
Molecular Events in the Development of Mesothelioma III: Chromosome and Gene Alterations, and Disruption of Cell Pathways 605
Molecular Events in the Development of Mesothelioma IV: Interference with Cell Cycle Control and Apoptosis: p53 607
Molecular Events in the Development of Mesothelioma V: Cell Cycle Control: pRb 607
Molecular Events in the Development of Mesothelioma VI: Interference with Cell Cycle Control: pRb and Simian Virus 40 607
Molecular Events in the Development of Mesothelioma VII: SV40: Other Effects 608
Molecular Events in the Development of Mesothelioma VIII: Interference with the p53 Pathway: The Role of Wilms’ Tumor 1 (WT1) 608
Molecular Events in the Development of Mesothelioma IX: NF2 Inactivation and Mesothelioma 609
Molecular Events in the Development of Mesothelioma X: FHIT 609
Molecular Events in the Development of Mesothelioma XI: Growth Factors/Cytokines 609
The Epidermal Growth Factor Receptor Transforming Growth Factor-a Loop 610
The Epidermal Growth Factor Receptor–Cyclooxygenase-2 Loop 611
Vascular Endothelial Growth Factor 612
Tumor Necrosis Factor-a 612
Inhibitors of Apoptosis Proteins and Tumor Necrosis Factor-a 612
Growth Factors and Extracellular Matrix Interaction 612
Molecular Events in the Development of Mesothelioma XII: Mesothelial Cell Kinetics and Proliferation 614
Pathologic Features of Malignant Pleural Mesothelioma 614
Macroscopic Features of Pleural Mesothelioma 614
Histologic Features and Classification of Pleural Mesothelioma 616
Epithelial Mesothelioma 616
Sarcomatoid Mesothelioma of the Pleura 623
Heterologous Differentiation in Sarcomatoid Malignant Mesotheliomas 625
Biphasic Malignant Mesothelioma 626
Transitional Mesothelioma 627
Pleomorphic Mesothelioma 628
Mesotheliomas Showing Variable Differentiation 628
Histochemical Features of Pleural Epithelial Mesothelioma 628
Immunohistochemical Features of Pleural Mesothelioma 630
Positive Immunohistochemical Markers for Mesothelial Cells 635
Calretinin 635
Cytokeratin 5/6 635
HBME-1 636
WT1 Protein 636
Podoplanin/D2-40 637
Thrombomodulin 637
Mesothelin 638
CD44S 638
Exclusionary Markers: Characteristically Positive in Adenocarcinomas and Negative in Mesotheliomas 638
Carcinoembryonic Antigen 638
Cluster of Differentiation 15 (CD15 Clone Leu-M1)639
Blood Group Antigen Lewisy (BG8 Clone) 639
Antibodies Directed Against Epithelial Cell Adhesion Molecule, Including Ber-EP4 and MOC31 639
B72.3 640
E-Cadherin 640
Thyroid Transcription Factor-1 640
Antibodies that Decorate both Mesothelial Cells and Carcinoma Cells with Reasonable Frequency: Cytokeratins, Epithelial Membrane Antigen, and CA125 641
Epithelial Membrane Antigen 641
CA125 642
Markers of Possible Use for the Distinction of Benign Mesothelial Proliferations Versus MM: EMA, bcl-2, p53, and CD56 (NCAM) 642
Epithelial Membrane Antigen 642
Bcl-2 642
p53 643
Neural Cell Adhesion Molecules: CD56 643
Intermediate Filament Proteins: Cytokeratins (Except CK5/6), Vimentin and Desmin 643
Cytokeratins 643
Coexpression of CKs and Vimentin 644
Desmin 644
Other Markers 644
Markers Related to Prognosis 645
Recommended Panel 645
Ultrastructural Features of Mesotheliomas 646
Cytogenetic and Molecular Features in Mesothelial Cell Proliferations 652
DNA Analysis and Proliferative Index in Malignant Mesothelioma 654
Rare/Unusual Mesotheliomas or Mesothelial Proliferations 654
Benign Mesothelial Inclusions in Lymph Nodes 654
Adenomatoid Tumor of the Pleura 655
Well-Differentiated Papillary Mesothelioma 656
Noninvasive Atypical Mesothelial Proliferations: The Concept of Mesothelioma In Situ and Discrimination Between Early-Stage Mesothelioma and Reactive Mesothelial Hyperplasia 657
Small Cell Mesothelioma 663
Deciduoid Mesothelioma 664
Mucin-Positive Epithelial Mesotheliomas 664
Gaucher Cell–Like Mesotheliomas 665
Multicystic Mesothelioma 665
Desmoplastic Sarcomatoid Mesothelioma of the Pleura and Its Distinction from Benign Fibrous Pleuritis 667
Lymphohistiocytoid Mesothelioma 672
Pleomorphic Mesothelioma 674
Localized Malignant Mesothelioma 675
Approach to Diagnosis/Differential Diagnosis 676
The Cytology of Malignant Mesothelioma 676
Rapport with Clinician 677
Macroscopic Appearance of Specimen and the Use of Tumor Markers 677
Specimen Preparation 677
Specimen Adequacy 678
General Aspects of Specimen Assessment 678
Features Indicative of Mesothelial Differentiation, and Discrimination Between Benign Mesothelial Hyperplasia and Malignant Mesothelioma 678
Ancillary Techniques used to Distinguish MM and Reactive Mesothelial Hyperplasia 681
Distinction Between Secondary Neoplasms Affecting the Pleura and Malignant Mesothelioma 682
Ancillary Techniques for the Distinction of Malignant Mesothelioma from Metastatic Neoplasms 683
Ancillary Techniques to Increase the Detection of Malignant cells in Effusion Fluids 683
Fine-Needle Aspiration in the Diagnosis of Malignant Mesothelioma 683
Secondary Malignant Neoplasms Affecting the Pleura 684
Pseudomesotheliomatous Tumors Affecting the Pleura Including Pseudomesotheliomatous Adenocarcinoma of Lung 685
Spindle Cell Carcinoma and Carcinosarcoma of Lung 687
Serosal-Surface Serous Papillary Tumors 687
Other Tumors that can Invade or Spread to the Pleura 688
Thymoma Affecting the Pleura 689
Other Neoplasms Arising in the Pleura 689
Spindle Cell Neoplasms 689
Epithelioid Hemangioendothelioma and Angiosarcoma of the Pleura 700
Primitive Neuroectodermal Tumor 703
Pleuropulmonary Blastoma 704
Pleural Lymphomas 704
Leukemic Involvement of the Pleura 705
Screening for Mesothelioma: Serum Levels of Soluble Mesothelin-Related Proteins and Osteopontin 706
Soluble Mesothelin-Related Proteins 706
Serum Osteopontin Levels 708
Chemical Analysis of Pleural Fluid and Pleural Neoplasms for Hyaluronic Acid 708
Clinicopathologic Correlations 709
Spread and Staging of Malignant Mesothelioma 709
Staging of Pleural Malignant Mesothelioma 713
Prognosis of Malignant Mesothelioma 713
References 717
44 Metastases to and from the Lung 750
Solitary Metastases 752
Cavitation 753
Endobronchial Metastases 754
Vascular Metastases 754
Lymphangitic Spread 759
Intrathoracic Nodal Spread 763
Pneumothorax and Bronchopleural Fistula in Malignancies 764
Pleural Metastases 764
Special Situations in Metastases in Lung 765
Lung 765
Sarcomas 766
Melanoma 766
Head and Neck 767
Thyroid 768
Breast 768
Liver 768
Colon and Rectum 768
Pancreas 769
Renal Cell Carcinoma 769
Ovarian Cancer 770
Uterus 770
Female Gestational Choriocarcinomas 770
Prostate 771
Testes 771
Metastases from the Lung 772
References 773
45 Cytopathology of Pulmonary Neoplasia 782
Respiratory Cytology Specimens: Acquisition Procedure, Collection, Processing, and Slide Preparation 783
Sputum 783
Specimen Procurement and Collection 783
Specimen Processing 783
Bronchial Washings 784
Specimen Procurement and Collection 784
Specimen Processing 784
Bronchial Brushings 784
Specimen Procurement and Collection 784
Specimen Processing 784
Bronchoalveolar Lavage 784
Specimen Procurement and Collection 784
Specimen Processing 785
Transbronchial Fine-Needle Aspirates 785
Specimen Procurement and Collection 785
Specimen Processing 785
Transthoracic Fine-Needle Aspirates 785
Specimen Procurement and Collection 785
Specimen Processing 785
Pleural Fluid 785
Specimen Procurement and Collection 786
Specimen Processing 786
Cell Block Preparation 786
Practical Classification of Pulmonary Neoplasms for Cytopathology 786
Malignant Neoplasms 786
Non–Small-Cell Carcinoma 786
Small Cell Carcinoma 795
Other Neuroendocrine Neoplasms 796
Mesothelioma 798
Lymphoma 800
Sarcoma 802
Endobronchial Carcinoma (Salivary Gland Type) 804
Premalignant Lesion: Squamous Cell Dysplasia 805
Benign Lesions 806
Pulmonary Hamartoma 806
Sclerosing Hemangioma 807
References 807
Index 811