Index
Note: page numbers in italicsrefer to figures and tables
AA amyloidosis 1337, 1338Abrikossoff’s tumor see granular
cell tumorsabscessblastomycosis 256Burkholderia cepacia 169Clostridium septicum 158Francisella tularensis 170hemolytic Streptococcus 164infection from
extra-pulmonarysources 151
Legionella micdadei 161Listeria monocytogenes 116Moraxella catarrhalis 171Nocardia asteroides 166Peptostreptococcus 159Staphylococcus aureus 163Yersinia pestis 175see also Wegener
granulomatosis,microabscesses
Acanthamoeba (amebiasis) 264,291, 294–5, 294
acetylcholine receptor (AChR)pathway 964
acid/alcohol-fast bacilli(AAFB) 207
acid b-galactosidase 423acid ceramidase deficiency
see Farber diseaseacid maltase deficiency
see Pompe diseaseacid sphingomyelinase 414, 416acinar dysplasia 82, 82Acinetobacter calcoaceticus
165, 166Acinetobacter pneumonia 148,
177acinic cell carcinoma 1138–41acinar cells 1139cell of origin 1138classification 1138clinical features 1138clinicopathologic correlation
1140
cytology 1140, 1140differential diagnosis 1140electron microscopy 1140genetics 1138glandular cells 1139histopathology 1138–9, 1139immunohistochemistry 1140intercalated ductal cells 1139macroscopic pathology 1138molecular findings 1138natural history 1140–1prognosis 1140–1radiographic features 1138typical carcinoid tumor
differential diagnosis 1167acinus 9, 10, 24–6, 81Actinomyces (actinomycosis)
pneumonia 177, 166acute capillary injury, antibody-
mediated rejection 781–2acute cellular rejection in lung
transplantation 769, 770,774–5, 779
airway inflammation withoutscarring 780–1
antibody-mediated rejectionassociation 782, 782
classification 778–81CMV pneumonitis distinction
777, 784diagnosis 775, 778–80, 781grades 774, 774–7, 776, 777,
778–81grading pitfalls 777–8morphological mimics 777,
777–8, 778, 779post-transplant
lymphoproliferativedisease – differentialdiagnosis 788–9
severe 777transbronchial biopsy 774
acute chest syndromesickle cell disease 680, 681
acute eosinophilic pneumonia(AEP) 577–80, 578
chronic eosinophilicpneumonia differentialdiagnosis 572, 580
clinical manifestations 577–8diagnostic criteria 577differential diagnosis 578–80diffuse alveolar damage 578–80histopathology 578, 580hyaline membranes 579laboratory findings 578natural history 580prognosis 580radiographic appearance 578smoking-related 579
acute febrile neutrophilicdermatosis 833
acute fibrinous organizingpneumonia (AFOP) 350,381–2, 382
dermatomyositis 827histological features 382polymyositis 827
acute interstitial pneumonia(AIP) 379–83, 381
clinical presentation 379differential diagnosis 382pathogenesis 382pathology 380–1, 381prognosis 383proliferative phase 380–1radiological findings 379–80treatment 383variants 381–2
acute lung injury (ALI) 342–58acute fibrinous organising
pneumonia 350acute phase 352airspace granulation tissue
polyps 347alveolar epithelial cells 355,
356alveolar epithelium damage
355alveolar re-epithelialization
356–7angiogenesis 356bronchoalveolar lavage 350clinical diagnosis 350–1coagulation system 355complications 344diffuse alveolar damage 342,
345–50
early disease 347edema fluid clearance 356electron microscopy 346endothelial cells 354–5, 355endothelial proliferation 356epidemiology 344etiology 342–4, 343exudative phase 345–6, 351–5fibroproliferative phase 355–7fibroblast migration 355fibroblastic focus 371fibrosis reversal 356hyaline membranes 345–6, 347incidence 344infection role 343, 350, 357inflammatory process
resolution 356intra-alveolar granulation
tissue removal 356macrophages 353, 354management 357–8mortality 344myofibroblast migration 355neutrophils 346, 351–3, 354non-pharmacological
interventions 358nonspecific interstitial
pneumonitis pattern 349open lung biopsy 351organizing 357, 450outcome 344pathogenesis 343–4, 351–7,
352, 357pathological features 345–50,
346, 348pathology 342pharmacological therapy
357–8platelets 354proliferative phase 346–9, 355–7radiographic features 344–5,
345repair process 187, 356–7resolution 357tracheal aspirates 350transbronchial biopsy 350–1
acute respiratory distresssyndrome (ARDS) 184,342–58
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acute silicoproteinosis (ASP)530–1, 531
acute vasculopathy, sickle celldisease 680
adenocarcinoma in situ (AIS)871, 889, 911, 1044, 1050
cytology 1058–9histopathology 1051–2morphological features 1065mucinous 1067–8, 1067,
1068non-mucinous 1052, 1053preinvasive lesion for lung
adenocarcinoma1049–50
prognosis 1066radiography 1065
adenoid cystic carcinoma1133–6
basaloid squamous cellcarcinoma differentialdiagnosis 1107–8
cell of origin 1133classification 1133clinical features 1133clinicopathologic correlation
1135cytology 1135, 1135differential diagnosis 1135electron microscopy 1135genetics 1133histopathology 1134, 1134immunohistochemistry 1135macroscopic pathology 1133,
1133metastases 1135, 1382, 1394molecular findings 1135natural history 1136prognosis 1136radiographic findings 1133typical carcinoid tumor
differential diagnosis1167
adenomatoid malformationssee congenitaladenomatoidmalformations
adenomatoid tumorof the peritoneum 1524of the pleura 1512, 1512, 1524
adenomatous rete testishyperplasia 1473
adenosquamous carcinoma1121–3, 1123
cell of origin 1121definition 1121differential diagnosis 1123genetics 1122–3histology 1121–2immunohistochemistry 1122incidence 1121mucoepidermoid carcinoma
differential diagnosis1132
prognosis/treatment 1123
adenovirus 193–4, 194lung transplantation 784–5, 784necrotizing hemorrhagic
pneumonitis 194pathology 193–4pneumonia 118, 182–3, 194smudge cells 194, 194ulcerative bronchiolitis 194
adiaspiromycosis 274, 275adrenal cortical carcinoma 1197,
1382adrenocorticotropic hormone
(ACTH) 972–3ectopic 973antiphospholipid syndrome
820coccidioidomycosis 262definition 342diagnosis 350diffuse alveolar damage 186–7,
350HSV infection 196malaria 298, 299radiographic features 345surfactant loss 26see also acute lung injury
aerodynamic equivalent diameter516
afferent autonomic nerves 12African–American people, lung
cancer 949agenon-small cell lung cancer
948tracheal stenosis 69
age-related EBV-associatedB-cell lymphoma 1344
aging of lungs 31–3, 624functional changes 32–3structural changes 31–2vascular remodeling 665–6
AIDS see HIV infectionair-crescent sign, angioinvasive–
disseminated aspergillosis235
air leaks 109–11air pollutionlung carcinoma 951–2see also environmental
pollutionairborne particle size 952airflow obstruction see airway
obstructionairspace development 1–4airspace enlargementdevelopment-related 623non-emphysematous 623starvation 623–4see also emphysema
airspace granulation tissuepolyps, ALI/ARDS 347
airway(s)anastomotic complications
in lung transplantation772–3
conducting 9development 1–4inflammation without scarring
in lung transplantation780–1
organization 7–8pneumonia 149–50wall thickness in asthma 567
airway-centered interstitialfibrosis 391, 464
airway disease, rheumatoidarthritis 811–13
airway obstructionclassification 607COPD 605, 607–8, 609, 612large airways 609small airways 609
airway surface liquid (ASL) 99,153
cystic fibrosis 99AL amyloidosis 1337, 1338Alaria 328alcohol ingestion, lung cancer
risk 958allergic bronchopulmonary
aspergillosis (ABPA)230–2, 598
bronchocentricgranulomatosis 576
Charcot–Leyden crystals 575diagnosis 232eosinophilic bronchiolitis
644histology 232middle lobe syndrome
633–4mucoid impaction of bronchi
575, 576pathology 574radiological appearance
232, 574allergic bronchopulmonary
fungal disease 573–5bronchiectasis 574–5bronchocentric
granulomatosis 575–6Charcot–Leyden crystals
574–5chronic eosinophilic
pneumonia differentialdiagnosis 571
clinical manifestations 573–4fungal hyphae 575‘gloved finger’ sign 574histopathology 574mucoid impaction of bronchi
574–5natural history 576–7organisms 573prognosis 576–7radiographic findings 574treatment 576
allergic granulomas, Churg–Strauss syndrome734, 735
allergic mucin 575allograft rejectionacute cellular rejection 769,
770, 774–5airway inflammationwithout scarring 780–1
antibody-mediated rejectionassociation 782
classification 778–81CMV pneumonitisdistinction 777, 784
diagnosis 778–80, 781grades 774, 774–7, 778–81grading pitfalls 777–8morphological mimics777, 777–8
post-transplantlymphoproliferativedisease differentialdiagnosis 788–9
antibody-mediated rejection768, 769, 781–3
bronchiolitis obliteranssyndrome 790–2
chronic vascular 792–3grading 774hyperacute rejection 771–2lung transplantation
hyperacute rejection 768altitude, hypoxic arteriopathy
686–8aluminum lung disease 549, 549alveolar adenoma 862–4, 862atypical adenomatous
hyperplasia differentialdiagnosis 917
cell of origin 862classification 862clinical features 862clinicopathologic correlation
864cytology 863, 863differential diagnosis 864electron microscopy 864genetics 862histopathology 862–3immunohistochemistry 863macroscopic pathology 862molecular findings 864natural history 864prognosis 864radiographic findings 862sclerosing hemangioma
differential diagnosis 872alveolar capillary barrier,
development 4alveolar capillary dysplasia
89–90, 89associated malformations 89genetic factors 90pulmonary vein misalignment
90alveolar damage, regional 382alveolar ducts 4, 24alveolar epithelial cells 24–6
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acute lung injury 355,356, 348
hyperplasia 348, 916see also pneumocytes
alveolar damage, regional 382alveolar epithelium 909–10carcinogenesis 909–10damage in ALI 355reactive proliferation 915–16
alveolar hemorrhage 828bland 816, 817
alveolar lipoproteinosis, silicosis530–1
alveolar macrophages 27, 390iron-laden 52smokers 387viral infections 184–5
alveolar proteinosis, aluminumlung disease 549
alveolar rhabdomyosarcoma 123,1514–5, 1515
alveolar septal fibrosis 386alveolar soft-part sarcoma
1379alveolar volume 7alveolidevelopment 4, 5, 6–7postnatal 6
organization 9–10pores of Kohn 26, 26wall 25
amiloride-sensitive epithelialsodium channels(ENaC) 25
aminoaciduria 427–8aminorex, plexogenic arteriopathy
induction 673amiodarone toxicity 590, 590electron microscopy 590Niemann–Pick disease
differential diagnosis416
nodules 591amniotic fluid, infection 115amebiasis 291–5, 292Balamuthia 291, 294–5free-living infections 294–5pleural infection 1425see also Acanthamoeba
(amebiasis), Entamoebahistolytica (amebiasis)
amosite cytotoxicity 1467amphiboles 512–13, 516, 1456,
1464asbestos bodies 517carcinogenic potential 1464fibers 516mesothelioma 1456
amphoterocin B 243, 244amyloid 1337calcifying fibrous tumor of the
pleura differentialdiagnosis 1430
deposition 814, 1326pleural 1423
senile pulmonary amyloid 32, 56tumor-associated 1340, 1340
amyloidosis 1340connective tissue disease 804diagnosis 1338immunohistochemistry 1339localized nodular 1338molecular pathology 1339nodular pulmonary 1331,
1339, 1339pleural fibrosis 1423pulmonary 1340, 1338rheumatoid disease 814, 1337,
1338Sjögren syndrome 1338, 1339systemic 1338, 1339tracheobronchial 1338transthyretin-derived 1337
anaerobic bacteria, pneumonia148, 155–75
Anaplasma phagocytophilumpneumonia 179
anaplastic large cell lymphoma(ALCL) 1342, 1356
anaplastic lymphoma kinase(ALK) gene, inflammatorymyofibroblastic tumor1277
anencephaly, ectopic glial tissue91
angioblasts 5angiocentric lymphoma 1335,
1337angiogenesis 4, 905–6, 925angiogenic squamous dysplasia
(ASD) 898angioimmunoblastic T-cell
lymphoma (AITL) 1346angiomatoid tumor of the
peritoneum 1524angiomyolipoma 1255–6, 1256angiomyolipoma 1249, 1250angiosarcomametastases 1383, 1392pleural 1518see also primary pulmonary
angiosarcomaAngiostrongylus
(angiostrongyliasis)313, 321, 321
angiotropic lymphomasee intravascular largeB-cell lymphoma
Anisakis (anisakiasis) 320ankylosing spondylitis 829,
829–30Ankylostoma duodenale 316Anopheles mosquito 297–8anthophyllite 1438anthracosis 217anthracotic pigmentation 536anthrax 177anti-basement membrane
antibodies, Goodpasturesyndrome 738, 739
antibody-mediated rejection(AMR) 768, 769, 781–3
acute cellular rejectionassociation 782
anti-HLA antibodies 782–3diagnostic criteria 782immunohistochemical criteria
782patterns of injury 781–2treatment 782–3
antigen detection,microbiological workup154–5
antigen presentation,mycobacterial infections213
antigen processing, modulationby mycobacterialinfections 212–13
antigenic drift/shift, influenzaA 187
antigenic stimulation, MALTlymphomas 1324
antineutrophil cytoplasmicantibodies (ANCA)
Churg–Strauss syndrome 732,735
diffuse alveolar hemorrhagein rheumatoid arthritis813
Goodpasture syndrome 739inflammatory bowel disease
834–5microscopic polyangiitis 731neutrophil interactions 711, 729pulmonary hemorrhage tests
711Wegener granulomatosis 713,
728, 834–5antineutrophil cytoplasmic
antibodies (ANCA)-associated diseases 711–40
drug-induced 713Goodpasture’s syndrome 382,
736–40microscopic polyangiitis 711,
729–31see also Churg–Strauss
syndrome, Wegenergranulomatosis
antioxidants, flavonoids 959antiphospholipid syndromeantibodies 819–20catastrophic 820, 820diffuse alveolar hemorrhage
816histologic features 820pulmonary hemorrhage
syndromes 741, 742pulmonary manifestations 820systemic lupus erythematosus
815, 819–20antiproteinase 3 622a-1-antitrypsin (A1AT)
deficiency 101, 606
antiproteinase 3 622diagnosis 620emphysema 619–20lung cancer risk 957panniculitis 622Wegener granulomatosis 714
a-1-antitrypsin (A1AT) molecule619
aortic sac 5APC gene mutations 865Apert syndrome, tracheal
stenosis 68apical cap 54, 1421–3, 1422, 1423differential diagnosis 1423epidemiology 1421fibrous 55histopathology 1422, 1422macroscopic pathology 1421–2pathogenesis 1422–3radiological findings 1421
aplasia of lung 74apoptosis 374, 903, 1465–6appetite suppressants 670, 673,
674argentiaffinity 1164arginine vasopressin (AVP) 972argyrophil nuclear organizer
regions (AgNOR) 1505Armillifer pentastomiasis 335,
334arsenic exposure, lung cancer
952–3arteriovenous malformations
(AVM) 1261–3clinical features 1261clinicopathologic correlation
1262differential diagnosis 1262hemangioma differential
diagnosis 1263hereditary hemorrhagic
telangiectasia 1261, 1262histopathology 1261macroscopic pathology 1261molecular findings 1261–2natural history 1262–3prognosis 1262–3pulmonary 1262radiographic findings 1261right-to-left shunting 1261treatment 1262–3
artefacts, biopsy 51–3, 51,52, 53
ASAH1 gene mutations 426asbestos 512–28atypical adenomatous
hyperplasia association921
background levels 513–16cell signaling 1464–5diffuse pleural fibrosis
association 1445environmental hazard 1460environmental sources 515,
1437–8
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asbestos (cont.)exposure 513in buildings 1458lag period to benignasbestos-associatedpleural effusionoccurrence 1443
lag period to diffuse pleuralfibrosis 1446
lag period to pleural plaqueformation 1440
mesothelioma 1457–61fiber burden 522–4lung cancer 526
fiber deposition/clearance 516fiber potency and lung
carcinoma 525–6latent period from exposure to
mesotheliomadevelopment 1464
lung carcinoma with exposure525–8, 953, 957
diagnosis 526–7electron microscopy 526,527–8
risk 526smoking 525, 526tissue analysis 527–8
lung content in referencepopulations 516
mesothelioma risk 526non-occupational risk 513–16,
953occupational risk 512–13oncogenesis mechanisms 1464paraoccupational exposure 515peritoneal mesothelioma 1461permissible exposure level 516reference population levels
513–16risk in industries/occupations
515route of travel to pleura 1440smokinglung cancer 525, 526synergism 953
types 513uncoated fibers 525in whitewash 1459see also amphiboles, chrysotile,
crocidolite, erionite,mesothelioma, tremolite
asbestos-airways disease 520asbestos bodies 516–18, 517,
518, 522amphibole 517characteristics 517, 517chrysotile 517detection 518diagnostic value 520rounded atelectasis 1451sheet silicate 548
asbestos body concentration 515exposure standards 516lung fiber content 515–16
regulatory activity 516asbestos fiberscounts in diffuse pleural
fibrosis 1447mesothelioma 1456–7pleural plaques 1437route of entry into pleura 1440translocation 1408see also amphiboles, chrysotile,
zeolitesasbestosis 371–2, 518–25asbestos-related lung cancer
526benign asbestos-associated
pleural effusion 1436–7,1443–4
benign asbestos-related pleuraldisease 1436–54
pleural plaques 1423, 1430,1436–43
cigarette smoke exposure520, 525
classification 520clinical features 519definition 520, 522diagnosis 520differential diagnosis 519,
521–2diffuse pleural fibrosis 1436–7,
1444–8calcifying fibrous tumor ofthe pleura differentialdiagnosis 1430
epidemiology 518–19fibrosis 520, 522–5pleural 1446uncoated fibers 525
folded lung 1436–7, 1448–51grading 522–5, 523, 524histopathologic definitions 522histopathology 520, 523ischemic heart disease 1437lung carcinoma association
525, 526macroscopic pathology 520,
522mechanisms 519pathogenesis 519pleural thickening 1446prognosis 525radiological features 519–20,
519risk 513smoking association 520, 525,
1439–40see also mesothelioma
Ascaris lumbricoides (ascariasis)314–16
bolus 315clinical features 314–15diagnosis 316eosinophilic reaction 316epidemiology 314life cycle 315organism 314, 315
pathology 315–16strongyloidiasis differential
diagnosis 317treatment 316
Ascaris suum 316ascites, hepatic cirrhosis 1411Asherson’s syndrome 820, 820Askin’s tumor 1170, 1520aspergilloma 232–3, 233, 234calcium oxalate deposition 233clinical features 232conidiospore formation 233diagnosis 233pathology 232–3sarcoidosis 482zonation 233
Aspergillus infection(aspergillosis) 228–39
allergic forms 230–2, 231angioinvasive–disseminated
235–7clinical features 235diagnosis 237hematogenousdissemination 237
hyphae 237pathology 236–7
angioinvasive–disseminatedaspergillosis 235–7
antibody tests 238aspergilloma 232–3biomarker detection 238bronchocentric
granulomatosis 230, 231calcium oxalate crystals 234Candida differential diagnosis
267–8chronic cavitary 235chronic pulmonary 234–5cavitary 234, 235clinical features 234–5diagnosis 235fibrosing 234, 235necrotizing 234, 235nomenclature 234pathology 235
clinical manifestations 230conidia phagocytosis 230conidiophore 228culture 238cystic fibrosis 230, 233diagnosis 237–8differential diagnosis 238diffuse pneumonic 237echinocandin therapy 239epidemiology 229forms 230fungus ball 229Fusarium infection differential
diagnosis 244galactomannan detection 238genetics 229–30b-D-glucan detection 238granulomatous pulmonary 237host response 230
hyphae 229immunocompromised patients
229incidence 227–8invasive 236lung transplantation 229,
785, 786marijuana-induced 598molecular diagnostics 238mortality rate 239neutropenia 229organisms 228–9pathogenesis 230pathophysiology 230pattern recognition receptors
229–30pleural effusion 1412pleurisy 1413pneumonia 116, 226prognosis 239radiographic features 233rheumatoid nodules 807suppurative 237tracheobronchial 237, 237, 312treatment 238–9triazole therapy 238–9voriconazole 239see also allergic
bronchopulmonaryaspergillosis (ABPA)
aspiration 632, 633foreign body-type cells 222lipids 632pathological response 632route of injury in pneumonia
149aspiration bronchiolitis 466–7,
466aspiration pneumonia 466–7, 466,
632, 790dermatomyositis/polymyositis
827sarcoidosis differential
diagnosis 492aspiration pneumonitis 632asteroid bodies 55sarcoidosis 485, 485
asthma 563–8acute bronchiolitis 640airway epithelium 564–5airway lumen 564airway wall thickness 567aspergillosis 230basement membrane 565–6blood vessels 566Charcot–Leyden crystals 564,
567, 567clinical manifestations 563collagen ultrastructure
565–6Creola bodies 567, 567Curschmann’s spirals 567, 568cytology 567eosinophilic bronchiolitis 644eosinophils 566
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epidemiology 563epithelial cell balls 567genetics 563goblet cell metaplasia 565histopathology 564–7inflammatory infiltrate 566laboratory findings 567lung cancer association 957lymphocytes 566macroscopic pathology 563–4mucus glands 567mucus plugs 563–4natural history 568neutrophils 566pathology 564, 565, 566plastic bronchitis 635prognosis 568pulmonary function tests 567radiological findings 563, 564T cells 566
atelectasis 51, 456biopsy artefact 51, 45see also rounded atelectasis
atopy, plastic bronchitis 635ATP-binding cassette A3
(ABCA3) gene mutations106
atrioventricular node cystictumor 1473
atypical adenomatoushyperplasia (AAH) 889,910–21
adenocarcinoma in situdifferential diagnosis1065
age factors 921alveolar adenoma differential
diagnosis 864angiogenesis 925asbestos exposure 921atypia 915carcinoembryonic antigen 926cell adhesion molecules 925–6cell cycle activity 922cell immortalization 925cell morphometry 922cellularity 915chromosome 3p loss 926chromosome 7 aneuploidy 926clinical relevance 927clonality 926–7concurrent lung
adenocarcinoma 921, 926cytofluorimetry 922cytology 915definition 912diagnosis 915differentialdiagnosis915–18,916estrogen receptors 925etiology 921extrathoracic malignancy
association 921gender association 921, 925genomic instability 926–7grading 915
ground-glass opacity 928histologic appearance
912–13, 913, 914, 914, 915hyperproliferation 922immunohistochemistry 914lesionslocation 912numbers 920, 920–1size 912, 915
lineage markers 925–6localized non-mucinous
bronchioloalveolarcarcinoma 922, 927, 928
macroscopic features 911–12,911, 912, 913
matrix metalloproteinases 926microscopic features 912–15molecular biology 921–2morphological features 1065multifocal disease 920multifocal micronodular
pneumocyte hyperplasiadifferential diagnosis 859
preinvasive lesion for lungadenocarcinoma 1049–50
prevalence 919–21, 920prognosis 927progression risk 927, 928, 929proliferation index 922radiographic features 911, 1065smoking association 921,
926–7subsequent invasion risk 927transcription factors 925tyrosine kinase signaling
pathway 923–5xenobiotic metabolizing
enzymes 926atypical mesothelial hyperplasia
(AMH) 1451, 1451–4,1452, 1508
diagnosis 1452–3differential diagnosis 1453survival 1453
autoantibodiesmixed connective tissue
disease 827scleroderma 820–1Sjögren syndrome 823, 825
autofluorescence bronchoscopy(AFB) 908
lung cancer 977specificity 909squamous dysplasia/
carcinoma-in-situ896–7, 908–9
autoimmune diseasepulmonary veno-occlusive
disease association 691sarcoidosis-like disease 490vasculitis 700see also named diseases
autoimmune pancreatitis,IgG4-related sclerosingdisease 1420
autopsy, specimen handling 45–7azygos lobe 8, 8Azzopardi phenomenon, small
cell lung carcinoma1162–3, 1163
B cell, immune response 154B-cell lymphomas 1324–43age-related EBV-associated
1344amyloidosis 1340Hodgkin’s lymphoma 1342,
1347immunohistochemical profiles
1329intravascular large B-cell
lymphoma 1336, 1337lymphomatoid granulomatosis
1331–6lymphoplasmacytic lymphoma
1331marginal zone lymphoma 825,
1324–9multiple myeloma 1340plasmacytoma 1342secondary pulmonary changes
1346see also diffuse large B-cell
lymphoma (DLBCL)B72.3 glycoprotein 1495Babesia (babesiosis) 300clinical features 300diagnosis 300epidemiology 300organisms 300pathology 300transmission 300vector 300
bacillary angiomatosis 177–8bacillary peliosis 177–8bacille Calmette–Guérin (BCG)
immunization 223Bacillus, pneumonia 177Bacillus anthracis 167, 177Bacillus cereus 168, 177Bacillus sphaericus 168bacterial infections 146–79barriers 153Gram-positive cocci 150hematogenous spread 152histologic features 155host defense 152–4inflammatory response 153–4innate immune response 154lung carcinoma 956–7lung transplantation 774management 154microbiological workup
154–5natural history 154necrotizing granuloma 150pathogenesis 152–4pneumonia 115–16, 146prognosis 154staining of bacteria 155
superinfection on viralinfections 185, 189–90
see also mycobacterialinfections, namedbacteria and diseases
Bacteroides fragilis pneumonia155, 158
bagpipe lung 75Balamuthia (amebiasis) 291,
294–5Balantidium coli 307baritosis 546barotrauma, cocaine abuse 597Bartonella pneumonia 177–8,
221basal cells 16–17hyperplasia 892–3, 892, 893
basal lamina see basementmembrane
basaloid carcinoma 1117–9cell of origin 1117cytology 1119differential diagnosis 1118histopathology 1117, 1118immunohistochemistry
1117–8, 1119pathology 1117prognosis 1118–9radiographic findings 1117
basement membrane 23, 27, 31bauxite mining 549Baylisascaris, toxocariasis
differential diagnosis 320Bcl-2 protein 904, 923, 1505Behçet syndrome 749–52,
831–2clinical manifestations 750, 750diagnostic criteria 749differential diagnosis 751–2epidemiology 749, 749exacerbations 832genetics 749–50heat-shock proteins 751hemoptysis 750histopathology 750–1infections 751macroscopic pathology 750natural history 752neutrophils 751pathogenesis 751pathology 750, 751, 831,
831–2, 832prognosis 752pulmonary artery aneurysms
831radiographic findings 750, 831remission 832
benign epithelial neoplasms847–79
alveolar adenoma 862–4bronchial papillomas 850–7multifocal micronodular
pneumocyte hyperplasia857–9
papillary adenoma 859–62
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benign epithelial neoplasms(cont.)pulmonary endometriosis
875–9pulmonary hyalinizing
granuloma 872–4sclerosing hemangioma
864–72benign lymphoid proliferations
1317–23in interstitial lung disease
1317–8marginal zone lymphoma
differential diagnosis 1329pulmonary 1318
benign metastasizing leiomyoma(BML) 1244–7, 1245,1246, 1398
cell of origin 1245classification 1245clinical features 1245clinicopathologic correlation
1247cytology 1247differential diagnosis 1247electron microscopy 1247genetics 1245histopathology 1245–7immunohistochemistry 1247lymphangioleiomyomatosis
differential diagnosis1254–5
macroscopic pathology 1245molecular findings 1247natural history 1247nodules 1245prognosis 1247racial factors 1245radiographic findings 1245treatment 1247
benzo[a]pyrene 950, 951Ber-EP4 glycoprotein 1495berylliosis 540, 541acute 540chronic 540, 541, 1424
berylliumexposure 540–1identification in lung
tissue 541lung cancer association 541sensitization 540toxicity 540
beryllium lymphocyteproliferation test 541
bevacizumab toxicity 592–3,1104
biglycan 621biopsyapplications 59–60artefacts 51–3, 62bronchial 59–60endobronchial 59–60inter-observer variability 62interface 49interpretation problems 62
large pleural 49misapplications 59–60open lung 59–60, 770problems 61–2surgical lung in interstitial
lung disease 366tissue problems 61–2transbronchial 59–61, 367transthoracic needle 59–60wedge 43–4see also video-assisted
thoracoscopic surgery(VATS)
Birbeck granules, Langerhans’cell histiocytosis 1348
bird-fancier’s lung 441, 446,467
Birt–Hogg–Dubé syndrome624–5, 1416
differential diagnosis 625genetics 624–5histology 625, 1418, 1419pathology 625, 625, 1418primary spontaneous
pneumothorax 1415radiographic appearance 625
bischloromethyl methyl ether(CMME) 953
black smoke measurement952
black spots, pleura 13, 31Blastomyces dermatitidis
(blastomycosis)228, 254–7
abscesses 198, 256antigen detection tests 256–7Candida differential diagnosis
267–8clinical features 254coccidioidomycosis differential
diagnosis 262cryptococcosis differential
diagnosis 262culture 256diagnosis 256–7differential diagnosis 257epidemiology 254histoplasmosis differential
diagnosis 250, 262immunocompromised
patients 257organism 254pathology 255–6, 255PCP differential diagnosis 272prognosis 257radiological appearance 254serological tests 256South American blastomycosis
differential diagnosis 264treatment 257see also Paracoccidioides
brasiliensis (SouthAmerican blastomycosis)
bleomycin toxicity 591–2Blesovsky syndrome 1448
blood cultures, microbiologicalworkup 154
blood group antigens 1496Bloom syndrome, lung cancer
risk 960blue bloaters, COPD 607blue bodies 56, 57blue clay 1459BMPR2 genehaploinsufficiency 670mutations 668–70, 674
body mass wasting, COPD 622–3bone marrow embolism 58, 58–9bone marrow transplantation,
amebiasis 294bone morphogenetic protein
4 (BMP-4) 5, 6bone morphogenetic protein
receptor 2 (BMPR2) 670pulmonary hypertension
668–70botryomycosis 163, 164, 165Neisseria mucosa 172pneumonia 176Staphylococcus aureus 164, 176with Streptococcus 165
brachial arch arteries 5BRAF gene mutation, lung
adenocarcinoma 1063brain natriuretic peptide (BNP),
pleural effusion incongestive heart failure1411
brain–thyroid–lung syndrome 1016Branhamella catarrhalis
see Moraxella catarrhalisbreast adenocarcinoma 1031breast carcinoma, metastases
1378, 1382, 1383,1389, 1395
breast mass, lymphangitic spread1385
bromocriptine, diffuse pleuralfibrosis induction 1445
bronchiabnormal origin/branching 73cartilage calcification 32compression 73congenital malformations 71–4development 1histology 15, 16mucus cell hyperplasia 19, 892mucus impaction 230–2allergic bronchopulmonaryfungal disease 574–5
organization 7, 8primary 8secondary 8segmental 9Sjögren syndrome 824–5submucosal elastosis 54tertiary 9
bronchi–biliary fistula 74bronchial arteries 30, 663anatomy 30, 665
angiography 98cystic fibrosis 98pathology 665post-obstructive vasculopathy
665therapeutic embolization 686
bronchial asthma, lungdevelopment 6
bronchial atresia 71–2, 72intralobar pulmonary
sequestration 83bronchial brushings, processing
41–2bronchial carcinogenesis
889–90animal models 890clonal patches 891etiology 891gene mutations 891loss of heterozygosity studies
907morphological changes 890tobacco smoking 891
bronchial circulatory system10–11
bronchial epithelium 15, 891bronchial gland collecting ducts,
oncocytic change 23bronchial inflammatory polyps
847–50cell of origin 847classification 847clinical features 848clinicopathologic correlation
849–50cytology 849differential diagnosis 850etiology 847histopathology 848–9macroscopic pathology 848natural history 850pathogenesis 847prognosis 850radiographic findings 848
bronchial isomerism syndromes73–4
bronchial lesions, pre-invasive 892bronchial papillomas 850–7glandular/glandular squamous
cell 855–7mixed squamous cell 855–7squamous cell papillomas
850–5bronchial pits, COPD 613bronchial probes 46, 47bronchial pseudoisomerism
68, 69bronchial smooth muscle 15bronchial stenosis 72bronchial submucosa 54bronchial submucosal glands,
oncocytic metaplasia 54bronchial veins 11, 663bronchial venous outflow 663bronchial venules 11
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bronchial washings, processing41–2
bronchiectasis 627–32allergic bronchopulmonary
fungal disease 574–5aspiration 632aspiration pneumonia 632bronchial probes 47bronchiolitis obliterans 794broncholithiasis 634–5carcinoid tumor 632classification 628–9clinical features 629course 632cystic fibrosis 47, 103definition 627epidemiology 629etiology 628inflammation 629middle lobe syndrome 632–4,
634pathology 629, 630, 631pathophysiology 629plastic bronchitis 635post-tuberculous 223prognosis 632radiology 629, 629rheumatoid arthritis 813slab section 47tracheobronchopathia
osteochondroplastica635–6
treatment 632bronchiolar columnar cell
dysplasia (BCCD) 911bronchiole(s)development 1, 4diseases with/without adjacent
parenchymal disease643–8
histology 15, 17organization 7Sjögren syndrome 824–5terminal 9
bronchiolectasisfollicular 1318middle lobe syndrome 634pathology 631rheumatoid arthritis 813
bronchiolitis 636–48acute 638–40, 639histopathology 639–40
adenovirus 194chronic 804, 813, 813, 825classification 637–8clinical features 636–7constrictive 637, 639, 641,
641–3, 642, 643neuroendocrine hyperplasia641
toxic agent ingestion 642–3COPD 609–11definition 636diffuse panbronchiolitis 644eosinophilic 644
granulomatous 645–6, 647herpetic 186HTLV-1 644hypersensitivity pneumonitis
450, 455infections 151, 638–9, 640lymphocytic 780, 780, 781, 781measles 193mineral dust disease 646, 647parainfluenza viruses 192, 192pathogenesis 609–11pathology 386proliferative 640, 640radiological findings 637respiratory syncytial virus
191, 191rheumatoid arthritis 809smokers’ 644viral infections 185–6Wegener granulomatosis 718see also follicular bronchiolitis,
obliterative bronchiolitisbronchiolitis interstitial
pneumonia 391, 464bronchiolitis obliterans
see obliterativebronchiolitis
bronchiolitis obliteransorganizing pneumonia(BOOP) see cryptogenicorganizing pneumonia(COP)
bronchiolitis obliteranssyndrome (BOS)
differential diagnosis 792grading 792histopathology 792inflammatory component 792lung-resident mesenchymal
stromal cells 4lung transplantation 782–3,
790–2treatment 792
bronchiolization of alveolisee peribronchiolarmetaplasia
bronchitisbronchial pits 613chronic in coal workers’
pneumoconiosis 536chronic in COPD 612–14epidemiology 612pathology 612–14pathophysiology 612tracheobronchialseromucinous glandchanges 614
COPD 609–11, 612–14eosinophilic 644non-asthmatic eosinophilic 568clinical manifestations 568histopathology 568natural history 568prognosis 568
pathogenesis 609–11
plastic 635purulent in cystic fibrosis 100
bronchoalveolar carcinoma 1044see also adenocarcinoma
in situ (AIS)bronchoalveolar epithelium
909–10, 915–16carcinogenesis 909–10
bronchoalveolar lavage (BAL)41–2, 770
bronchoalveolar stem cells(BASC) 7
bronchocentric granulomatosis221–2, 577, 729
aspergillosis 230, 231, 575–6,576
bronchogenic carcinoma 531–2bronchogenic cysts 77–8, 78diagnosis 77etiology/location 77–8presentation 77
broncholithiasis 634–5, 635bronchomalacia 72–3associated anomalies 72–3management 73pathology 72
bronchoplastic resection 45–7bronchopneumonia 150, 774tuberculous 217, 217
bronchopulmonary chondroma1227
bronchopulmonary dysplasia106–9
chronic stage 108early exudative phase 107extremely low gestational age 6fibrotic cystic lung 106genetic factors 109hyaline membrane disease 106new 106–7, 108old 106–8pathogenesis 108–9pathology 107–8, 108prevalence 107prognosis 109pulmonary hypertension 108severe 107subacute fibroproliferative
stage 108surfactant absence 26thyroid transcription factor 1
1016Wilson-Mikity syndrome
differential diagnosis 109bronchopulmonary foregut
malformation 85bronchopulmonary segments
8–9, 9, 10bronchopulmonary sepsis,
chronic 223bronchoscopy 9bronchus-associated lymphoid
tissue (BALT) 15, 24,1316, 1317
acquired 1317
acute cellular rejectionmorphological mimic777, 778
hyperplasia 812inducible 1317lymphoid tissue 24smoker 15
Brucella, pneumonia 178Brucella melitensis 169Brugia malayi 308–9, 313brush cells 15, 22–3, 24distribution 22function 23microvilli 22, 22structure 22
bubble artefact, biopsy 52–3, 53Burkholderia cepacia 169, 178cystic fibrosis 99–100, 101, 178
Burkholderia pseudomalleipneumonia 169, 178
busulfan toxicity 591, 592
C-fibers 12C-mesenchymal–epithelial
transitional factor(C-MET) 1064, 1529
C-reactive protein (CRP) 1412cadherins see E-cadherin,
N-cadherincadmium pneumonitis 550calcified pleural granulomas
1430calcifying fibrous tumor of the
pleura 1429, 1429–30clinical features 1429differential diagnosis 1429–30pathology 1429prognosis 1430
calcitonin 1165calcium oxalate crystals 56, 486calretinin 1496–7, 1502–3Candida (candidiasis) 264–8antibody detection 267antigen detection 267ascending infection 115blood culture 267clinical features 265cystic fibrosis 265diagnosis 266–8differential diagnosis 267–8disseminated disease 265endobronchial spread 265epidemiology 264–5fungal autofluorescence 266germ tube production 267b-D-glucan detection 267hematogenous spread 265immune response 264immunocompromised patients
265incidence 227–8invasive 265latex agglutination test 267lung transplantation 785miliary 266
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Candida (candidiasis) (cont.)molecular diagnostic methods
267organism 264pathogen recognition 264–5pathogenesis 264–5pathology 265–6pneumonia 115, 116, 264, 266prognosis 268radiological appearance 265sepsis/septic shock 265species complexes 264sputum culture 267systemic 265treatment 268
Candida albicans 264Candida dubliniensis 264Candida glabrata 264, 265Histoplasma capsulatum var.
capsulatum differentialdiagnosis 249
pathology 266PCP differential diagnosis 272
Candida krusei 264Candida parapsilosis 264, 265Candida tropicalis 264, 265cannabis abuse 597–8Capillaria (capillariasis) 320–1capillariesacute injury in antibody-
mediated rejection 781–2development 5lipid in 112
capillaritis 740–5clinical presentation 740connective tissue disease
pattern of involvement804
diagnosis 741diffuse alveolar hemorrhage 816laboratory studies 741radiographic findings 740–1systemic lupus erythematosus
742, 815Wegener’s granulomatosis 742
capillary network, development 5Caplan syndrome
see rheumatoidpneumoconiosis (RP)
carbon electrode makers 536carbon fibers 551–3carbon monoxide, lung
adenocarcinomaassociation 952
carbon nanotubes 553carborundum 544carcinoembryonic antigen (CEA)
926, 1495carcinogenesis 928–9alveolar epithelium 909–10peripheral lung
adenocarcinogenesismolecular biology 921–2
peripheral lung epithelium909–10
scar cancer theory 910see also bronchial
carcinogenesiscarcinogens 954, 955cigarette smoke 950, 951
carcinoid syndrome 1153carcinoid tumor 1155acinic cell carcinoma
differential diagnosis 1140atypical 1019, 1152, 1160clinical features 1153cytology 1160, 1160, 1161differential diagnosis 1167electron microscopy 1166histopathology 1160natural history 1169prognosis 1169typical carcinoid tumordifferential diagnosis1168
bronchiectasis 632classification 1151–2clear cell 1121, 1138cytology 1158, 1159, 1160dense core vesicles 1151diffuse idiopathic pulmonary
neuroendocrine cellhyperplasia 1176
fetal adenocarcinomadifferential diagnosis1074
fusiform cells 1157genetics 1166granular cell tumor differential
diagnosis 1242growth pattern 1157immunohistochemistry 1165macroscopic pathology 1155,
1155marginal zone lymphoma
differential diagnosis1328–9
melanin pigment 1158neuroendocrine markers 1027oncocytic 1158papillary/acinar architecture
1158plasmacytoma differential
diagnosis 1341primary pulmonary glomus
tumor differentialdiagnosis 1249
radiographic findings 1153–5,1155
sclerosing hemangiomadifferential diagnosis 872
small cell lung carcinomadifferential diagnosis1169
thyroid transcription factor 1expression 1018, 1019,1165
TNM classification 1012tumorlet differential diagnosis
1176–7, 1177
typical 1176atypical carcinoid tumordifferential diagnosis1168
clinical features 1152–3cytology 1159–60, 1166differential diagnosis 1167electron microscopy 1166histopathology 1157–60natural history 1169prognosis 1169variants 1157
carcinoid tumorlets see tumorletscarcinoma-in-situ (CIS)
see squamous dysplasia/carcinoma-in-situ(SD/CIS)
carcinomatous pulmonaryendarteritis 1389–90
carcinosarcoma 1197–205, 1201basaloid squamous cell
carcinoma 1198blastomatoid 1198, 1200–1,
1203–4, 1202, 1203clinical features 1202, 1203pathological features 1202,1203
pulmonary blastomadifferential diagnosis1203, 1214–5
clinical features 1198, 1199cytology 1203definition 1197–8differential diagnosis 1204electron microscopy 1204epidemiology 1200epithelial component 1198,
1203histopathology 1198–203, 1200immunohistochemistry 1203–4macroscopic pathology 1198metastases 1203molecular findings 1204natural history 1204–5pathological features 1199pleomorphic adenoma
differential diagnosis1143–4
primary pulmonarychondrosarcomadifferential diagnosis1238–9
primary pulmonary osteogenicsarcoma differentialdiagnosis 1236
prognosis 1204–5, 1204radiographic findings 1198,
1200sarcomatous elements
1201–3smoking 1198
cardiophrenic recess, blunting1412–3
Carney’s triad, pulmonarychondroma 1237
Carrington’s pneumonia 570–1caspases 1465Castleman disease 1268, 1322–3hyaline-vascular type 1322–3,
1323localized 1322–3mesothelioma differential
diagnosis 1514multicentric 1316, 1323clinical features 1323pathology 1323, 1324primary effusion lymphoma1355
plasma cell variant 1323pulmonary nodular lymphoid
hyperplasia differentialdiagnosis 1321–2
b-catenin gene mutation 1204,1212–3
cationic amino acid (CAA) 427,428
CD1a 1349, 1350CD44v6 906, 925–6CD57 1164CD205 see DEC205cdk inhibitors, mesothelioma
1468CDK4/cyclin D1 pathway
904–5cell adhesion molecules, atypical
adenomatous hyperplasia925–6
cell-associated sialomucins,mesothelium 1409
cell immortalization 906cellular immunity, giant cell
arteritis 746central nervous system (CNS),
paraneoplastic syndrome973–4
centrilobular fibrosis 467cerebral tissue, embolic
phenomena 90–1cervical cancer, metastases 1398cervical lymph nodes, metastases
1394cestodes 328–35cetuximab 593Chagas disease see Trypanosoma
cruzi (Chagas disease)Charcot–Leyden crystals 327allergic bronchopulmonary
aspergillosis 574–5, 575asthma 564, 567, 567chronic eosinophilic
pneumonia 569, 569treatment 328
chemodectoma see minutepulmonarymeningothelial-likenodules (MPMN)
chemokines 1317, 1412chemotherapyimmunosuppressive effects
1348
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pulmonary veno-occlusivedisease 691
with radiation therapy on lungcarcinoma 594–5
childrenepituberculosis 218lung transplantation
indications 768mesothelioma 1460metastases 1376–7mucoepidermoid carcinoma
1127non-small cell lung cancer 948parainfluenza virus 192passive smoking 950pleuropulmonary blastoma
118–23, 1215pulmonary alveolar
proteinosis 395pulmonary
rhabdomyosarcoma 1242respiratory papillomatosis 850respiratory syncytial virus 191see also infants
Chlamydia trachomatis 159pneumonia 116, 175
Chlamydiaceae pneumonia 175Chlamydophila (Chlamydia)
pneumoniae 147, 175, 957Chlamydophila (Chlamydia)
psittaci 148, 175chloromethyl methyl ether
(CMME) 953cholesterol effusion 1429cholesterol granuloma 465, 465chondrosarcomametastatic 1380primary pulmonarychondrosarcomadifferential diagnosis1238–9
pulmonary chondromadifferential diagnosis 1237
myxoid 1521see also primary pulmonary
chondrosarcomachordoma, metastases 1387chorioamnionitis 115choriocarcinoma 1197metastases 1384, 1399
CHRNA3/5 alpha-nicotinicacetylcholine receptor957
CHRNA 3 gene 965Chromobacterium violaceum 170non-caseating granuloma 170pneumonia 178
chromogranin 21, 1026, 1027, 1164chromosomal aneusomy,
squamous dysplasia/carcinoma-in-situ 907
chromosome 3ploss in atypical adenomatous
hyperplasia 926smoking 907
chromosome 7 aneuploidy,atypical adenomatoushyperplasia 926
chromosome 15q, lung cancerassociation 964
chronic eosinophilic pneumonia(CEP) 568–73, 588
acute eosinophilic pneumoniadifferential diagnosis 580
associations 571causes 571Charcot–Leyden crystals 569,
569Churg–Strauss syndrome 569,
734, 736clinical manifestations 568desquamative interstitial
pneumonia differentialdiagnosis 573
differential diagnosis 570–3eosinophils 569–70giant cells 569, 571histopathology 569–70, 569,
570, 571with lung cancer 572macrophages 569natural history 573prognosis 573radiographic findings 568–9,
569usual interstitial pneumonia
572chronic lung disease of
prematurity 107chronic lymphocytic leukemia/
small lymphocyticlymphoma (CLL/SLL)1347
chronic myeloproliferativedisorders, pulmonaryhypertension 684–6
chronic obstructive pulmonarydisease (COPD) 532–3,605–23
A1AT deficiency 606, 619–20,622
diagnosis 620acute bronchiolitis 640airway obstruction 605, 607–8,
609, 612large airways 609small airways 609
airway wall thickness 567basement membrane 612–13blue bloaters 607body mass wasting 622–3bronchial glands 613bronchial pits 613bronchiolar muscular
hypertrophy 610bronchitis/bronchiolitis 609–11chronic bronchitis 612–14epidemiology 612pathology 612–14
clinical manifestations 607–8
clinical phenotypes 607cor pulmonale 621–2course 611–12diaphragmatic dysfunction
623disorders 605emphysema 614–21A1AT deficiency 619–20classification 615–18genetics 607immunological process 621pathogenesis 620–1severity estimation 618–19smoking 620, 621
epidemiology 605–6, 606, 946gender 605–6genetics 606–7, 607hypoxic arteriopathy 688inflammation 611lung cancer risk 957lung transplantation 768macrophages 611Moraxella catarrhalis 147mucins 612mucus plugs 564, 610muscle dysfunction 623neutrophils 611osteoporosis 622panniculitis 622pathological changes 605, 609,
611, 613pathophysiology 609pink puffers 607prevalence 605–6prognosis 611–12pulmonary function tests 607–8pulmonary hypertension 621pulmonary vascular disease
621radiographic findings 608–9Reid index 614right ventricular dysfunction
621–2secondary pneumothorax
1415–6small vessel vasculitis 622smoking 609–11, 620, 621sporotrichosis 272susceptibility chromosomal
loci 957systemic effects 621–3systemic inflammatory
reaction 623tracheobronchial
seromucinous glandchanges 614
treatment 612chronic recurrent
thromboembolic disease(CRPE) 768
chronic thromboembolicpulmonary hypertension(CTEPH) 679–86
classification 679definition 679
epidemiology 679–80risk factors 679–80
chronic vascular rejection 792–3Chrysosporium parvum var.
crescenssee adiaspiromycosis
chrysotile 513asbestos bodies 517–18, 517cytotoxicity 1467environmental pollution 1437,
1438fibers 516mesothelioma 1456–7pleural plaque induction 1439
Churg–Strauss syndrome 731–6acute eosinophilic pneumonia
differential diagnosis 580airway involvement 733–4allergic granulomas 734, 735ANCA 732, 735asthma medication-induced 735autoantibodies 711chronic eosinophilic
pneumoniaassociation 569differential diagnosis 572
classification 731–2clinical manifestations 732–3,
733cytology 735definitions 732differential diagnosis 221,
310–11, 572, 734, 735–6,744–5
drug-induced 589eosinophils 734epidemiology 732filarial disease differential
diagnosis 310–11genetics 732histopathology 734, 734, 735humoral immunity 735IL-10 haplotype 732laboratory findings 735leukotriene receptor
antagonists 735macroscopic pathology 734,
734natural history 736pathogenesis 735peripheral neuropathies 733phases 732–3polyarteritis nodosa differential
diagnosis 744–5prognosis 736radiographic findings 733–4,
733, 734subgroups 732T-cell subpopulations 735tuberculosis differential
diagnosis 221vasculitis 734, 736
chylothorax 1428–9, 1428diffuse pulmonary
lymphangiomatosis 1259
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chylothorax (cont.)lymphangioleiomyomatosis
1254, 1255cilia 18, 98abnormalities 96, 96
ciliated cells 15–16function 16structure 16
Clara cell secretory protein(CCSP) 7, 910, 1025
Clara cells see Club (Clara) cellsclear cell(s) see pulmonary
neuroendocrine cells(PNCs)
clear cell carcinoid 1121, 1138clear cell carcinoma 1120–1,
1121clear cell renal cell carcinoma 1258clear cell sarcoma 1258, 1489clear cell tumor of the lung
(CCTL) 1256–8, 1257acinic cell carcinoma
differential diagnosis1140
cell of origin 1256classification 1256clear cell carcinoma
differential diagnosis1121
clear cell squamous cellcarcinoma differentialdiagnosis 1106
clinical features 1256clinicopathologic correlation
1258cytology 1257–8differential diagnosis 872,
1029, 1106, 1121, 1138,1229, 1258, 1397
electron microscopy 1258epithelial–myoepithelial
carcinoma differentialdiagnosis 1138
histopathology 1257immunohistochemistry 1258macroscopic pathology 1256–7minute pulmonary
meningothelial-likenodule differentialdiagnosis 1229
molecular findings 1258natural history 1258prognosis 1258radiographic findings 1256renal cell carcinoma
metastases differentialdiagnosis 1397
sclerosing hemangiomadifferential diagnosis 872
clonal patches, bronchialcarcinogenesis 891
Clostridium, pneumonia 155–75Clostridium perfringens
pneumonia 155, 158Clostridium septicum 158
abscess 158pneumonia 155–75
Club (Clara) cells 7, 15, 17–18, 910electron microscopy 19function 17histology 18invasive lung adenocarcinoma
1055subsets 17–18
clubbing of fingers/toes 973mesothelioma 1469small cell lung carcinoma 1153solitary fibrous tumor of the
pleura 1435coagulation system, acute lung
injury 355coal bodies, ferruginized 536coal/coalmine dust 532–6cigarette smoking additive
effect 536dust reduction 533quartz content 533ranking 533
coal dust macule 533–4coal dust nodules 534coal workers’ pneumoconiosis
(CWP) 532–3, 534chronic bronchitis 536classification 533clinical features 533complicated 534differential diagnosis 535–6diffuse interstitial fibrosis 536emphysema 534, 536epidemiology 533lung carcinoma 536macular lesions 533–4nodular lesions 534pathogenesis 533pathology 533–4, 534, 535, 535progressive massive fibrosis
533, 534, 535–6radiological appearance 533
cobalt lung disease see hard metallung disease
cocaine abuse 596–7barotrauma 597pathogenesis 597pathology 596, 596toxicity 596
Coccidioides immitis(coccidioidomycosis)257–62, 258
antigen detection tests 262blastomycosis differential
diagnosis 257chronic pulmonary infection
259clinical features 259–61coccidioidoma 259–60complement fixation test 261–2culture 261diagnosis 261–2differential diagnosis 257, 262,
264
disseminated disease 261, 261epidemiology 257–9immunocompromised patients
260immunodiffusion tests 261latex particle agglutination
test 262miliary 261, 262necrotizing granulomas 259organism 257pathology 259–61primary pulmonary infection
259prognosis 262progressive pulmonary disease
260, 260radiological appearance 259serological tests 261–2skin tests 261South American blastomycosis
differential diagnosis 264treatment 262
coccidioidoma 259–60cold agglutinins, diffuse
panbronchiolitis 644colorectal adenocarcinoma,
metastases 1385, 1396,1396
colorectal carcinomametastatic 1031, 1032, 1396thyroid transcription factor 1
expression 1019common variable
immunodeficiency (CVID)lymphoma 1344primary effusion lymphoma
1355sarcoidosis-like disease 490
computed tomography (CT),micro-CT scanning 48
congenital adenomatoidmalformations 78–82, 79,1016
alveolar adenoma differentialdiagnosis 864
classification 78, 79–82cystic lesions 77, 79hemangioma differential
diagnosis 1263intralobar pulmonary
sequestration 83large cyst type 79–80, 79lung adenocarcinoma
association 1047malignancy risk 79management 78, 81–2mucigenic epithelium 80peripheral lung cyst 81presentation 78prevalence 78prognosis 81–2small cyst type 80, 80solid adenomatoid
malformation 80–1, 81subtypes 79–82, 81
congenital cystic lung 89congenital heart diseasewith hypo-/hyper-perfusion
693–6left-to-right shunts 696malformations with
pulmonary hyperflow696–7
plexogenic arteriopathy 673,697
pulmonary hypertension 667–8,696–7
pulmonary hypoperfusion 696congenital high airway
obstruction syndrome(CHAOS) 86
congenital lobar emphysema85–6, 85, 86
congenital lymphangiectasia87–8, 86
congenital malformations 66–95alveolar capillary dysplasia
89–90bronchus 71–4classification 76congenital lobar emphysema
85–6congenital pulmonary
lymphangiectasis 87–8diaphragmatic eventration
93–5diaphragmatic hernia 94–5enteric cysts 88–9incidence 66isomerism subtypes 74lung 74–95polyalveolar lobe 85pulmonary cystic disease
75–82pulmonary hyperplasia 86–7pulmonary hypoplasia 91–3pulmonary sequestration 82–4tracheal 66–71
congenital peribronchialmyofibroblastic tumor124–5, 125
congenital pulmonary airwaymalformation (CPAM),type 4 123
congenital pulmonarylymphangiectasis 87–8
diagnosis 87–8management 88
congestive heart failure, pleuraleffusion 1410–1
congestive vasculopathy 665, 692arterialization of veins 689–90associated conditions 689causative factors 689epidemiology 689histopathology 689–91medial hyperplasia 690pulmonary capillary
hemangiomatosisdifferential diagnosis 693
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pulmonary hypertension 667,683–4, 689–91
pulmonary infarction 690–1pulmonary veno-occlusive
disease differentialdiagnosis 693
thrombotic arteriopathy 683–4vascular lesions 691
connective tissue 10, 31connective tissue disease 804–35acute exacerbation 804genetics 806idiopathic interstitial
pneumonia 806inherited 428–32interstitial lung disease
patterns 378lung cancer association 958lymphoid interstitial
pneumonia association463
nonspecific interstitialpneumonia pattern 378,379
patterns of pleuropulmonaryinvolvement 804, 805–6
pleural 1425–6pneumonia 371pulmonary hypertension 392,
697–8pulmonary veno-occlusive
disease association 691secondary complications 804undifferentiated 828–9, 829diagnostic criteria 829interstitial lung disease 829nonspecific interstitialpneumonia pattern 829
pathology 829see also named diseases and
conditionscor pulmonale, COPD 621–2cord funisitis 115coronary artery disease, pleural
plaque association 1436–7Coronavirus, SARS 182, 190corpora amylacea 56, 57corundum 549cotinine clearance 950–1coughHering Breuer reflex 1436solitary fibrous tumor of the
pleura 1435–6Coxiella burnetii pneumonia
148, 179craniosynostosis syndromes,
tracheal stenosis 68Creola bodies, asthma 567, 567CREST syndrome 697–8, 820,
822, 823cri du chat syndrome, lung
herniation 75crocidolite 1438, 1440, 1443,
1444, 1447, 1454, 1456,1459, 1459, 1467
Crohn’s disease 833–5, 834crospovidone 599, 600croup, parainfluenza virus 192Crouzon’s disease, tracheal
stenosis 68crush artefact, biopsy 52, 52crush phenomenon, small cell
lung carcinoma 1162–3,1167
Cryptococcus neoformans(cryptococcosis) 250–4
antigen detection tests 253–4Candida differential diagnosis
267–8clinical features 250–2coccidioidomycosis differential
diagnosis 262coin lesion 252culture 252–3diagnosis 252–4differential diagnosis 254, 262,
264, 267–8, 272epidemiology 250nodules 252organism 250pathology 251, 252PCP differential diagnosis 272pneumonia 253prognosis 254radiological presentation 252,
252serological tests 253South American blastomycosis
differential diagnosis 264tissue reaction 252treatment 254
cryptogenic fibrosing alveolitissee usual interstitialpneumonia (UIP)
cryptogenic organizing pneumonia(COP) 367, 463, 572
hypersensitivity pneumonitis455
lymphoid proliferation 1318Cryptosporidium
(cryptosporidiosis) 305–7bronchial 307clinical features 306diagnosis 307epidemiology 305–6fecal detection 306organism 306pathology 306schizogony 234treatment 307
Cryptosporidium hominis 306Cryptosporidium parvum 306Cryptostroma corticale spores 453crystal-storing histiocytosis
412, 413Curschmann’s spirals, asthma
567, 568Cushing syndrome 971, 972–3carcinoid tumor 1153small cell lung carcinoma 1153
CXCR3 chemokine receptor 28CXCR4 chemokine receptor
28, 1235cyclin D1 904, 909, 923cyclins, mesothelioma 1468cyclo-oxygenase 2 (COX-2) 906Cyclospora cayetanensis 307CYP1A1 see cytochrome P450
1A1cystic echinococcosis 328–34cystic fibrosis (CF) 97–101airway pathophysiology 99airway pus 99airway surface liquid
movement disruption 99aspergillosis 230, 233bronchial arteries 98bronchial wall 102bronchiectasis 47, 103Burkholderia cepacia 99–100,
101, 178Candida infection 265cartilage destruction 103changes in care 97clinical presentation 97–8clinical signs 98defect 99diagnosis 97genetics 98hilar lymph node 103histology/histopathogenesis
100–1infections 99–100, 178inflammation 99–100lung development 6lung disease progression 97–8mucosal gland hyperplasia 102pediatric lung transplantation
768pneumothorax differential
diagnosis 1419Pseudomonas aeruginosa
infection 99, 100pulmonary hypertension 99, 103purulent bronchitis 100secondary pneumothorax
1415–6serous gland hyperplasia 102sputum 97submucosal glands 99
cystic fibrosis transmembranereceptor (CFTR) 18, 98
cystic pleuro-pulmonaryblastoma (CPPB) 79
cysticercosis 333, 333–4cytochrome P450 1A1lung cancer risk 960pleomorphic carcinoma 1191–2polymorphisms 891, 949
cytochrome P450 enzymes 949cigarette smoke metabolism
950, 951cytokeratin(s)immunohistochemistry 1027mesothelioma 1498
biphasic 1502lung adenocarcinomadistinction 1496
neuroendocrine tumors 1165preinvasive lesions 906–7sarcomatoid mesothelioma
1502cytokeratin 5/6lung adenocarcinoma
immunohistochemistry1061
mesothelioma diagnosis 1498sarcomatoid mesothelioma
1502squamous cell carcinoma
immunohistochemistry1103
cytokeratin 7, 1020, 1028cytokeratin 20, 1028cytokinesBALT 1317Langerhans’ cell histiocytosis
1351cytology specimen processing
41–2cytomegalovirus (CMV) 116–17,
194–5alveolar type II cells 195antigen 196chronic lung disease in infant
117clinical signs 195Cowdry type B inclusions 195cytoplasmic inclusions 195,
196, 784diagnosis 195, 783disease 783HIV infection 195, 196immunosuppression 195infection 783–4inflammatory response 784tissue invasive disease 783viral syndrome 783
cytomegalovirus (CMV)pneumonitis 184, 783
acute cellular rejectionmorphological mimic777, 784
lung transplantation 777,783–4, 784
miliary infection 195organ transplantation patients
195cytotoxic drugs, lymphoma
association 1345
D2-40, mesothelioma diagnosis1498–9, 1509
DEC205 (CD205) 28decorin 621b-defensin 2 (b-D2) 18–19defensins, viral infections 184delayed-type hypersensitivity
reactions, mycobacterialinfections 213, 217
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dendritic cell(s) 27–8histoplasmosis infection 245myeloid 27–8plasmacytoid 27–8
dendritic cell sarcoma, follicular1352, 1352
dense core vesicles (DCV) 21, 1151carcinoid tumor/small cell
lung carcinoma 1151dental technician’s
pneumoconiosis 545, 545,546, 547
dermatofibrosarcomaprotruberans, metastases1392, 1400–1
dermatomyositis 825–7acute fibrinous organizing
pneumonia 827amyopathic 825anti-Jo-1 826aspiration pneumonia 827diffuse alveolar damage 826interstitial lung disease 826lung carcinoma 827, 958nonspecific interstitial
pneumonia pattern 826organizing pneumonia pattern
826, 826paraneoplastic syndrome
974–5pathology 825prognosis 826usual interstitial pneumonia
pattern 826desmin 1453, 1505desmocollin-3 1029desmoid tumor 1521extra-abdominal and solitary
fibrous tumor of thepleura differentialdiagnosis 1435
primary pleuropulmonary 1520desmoplastic small round cell
tumor 1171, 1518, 1519,1171
desmosomes, squamous cellcarcinoma 1103
desquamative interstitialpneumonia (DIP)367, 385, 388–91
chronic eosinophilicpneumonia differentialdiagnosis 573
clinical presentation 388differential diagnosis 389–90Gaucher disease differential
diagnosis 412histopathology 388–9, 390natural history 390pathogenesis 390prognosis 390radiological findings 388, 388
desquamative interstitialpneumonia-likereaction 388
desquamative interstitialpneumonitis 114
development of lung 1–7airspace 1–4airway 1–4alveolar stage 3, 4, 5canalicular stage 4genetic factors 5–6postnatal 6pseudoglandular stage 2, 1–4radial count estimation 4regulation 5–6saccular stage 4sex effect on growth 6stages 3vascular 4–5vascular remodeling 665–6
developmental delay 6diaphragmagenesis/aplasia 95dysfunction in COPD 623eventration 93–5, 94
diaphragmatic hernia 94–5, 95pathology 95presentation 94–5prognosis 95pulmonary hypoplasia 98tracheal stenosis 68
diaphragmatic plaque 1441DICER genemutations 122–3upregulation in localized
non-mucinousbronchioloalveolarcarcinoma 927
dietgenetic makeup 958lung cancer 958–60
dietary restriction, lung cancer 960diffuse alveolar damage (DAD)
379–83acute eosinophilic pneumonia
578–80acute exacerbation of
idiopathic pulmonaryfibrosis 384
acute lung injury/ARDS 342,345–50
acute lupus pneumonitis 815amiodarone toxicity 590bleomycin toxicity 592connective tissue disease 804dermatomyositis 826drug-induced lung disease
586–7, 589exudative phase 379–80, 380fibroproliferative phase 348histological features 381hyaline membrane 186influenza 189–90, 189intravascular thrombosis 58late stage 381measles 193mixed connective tissue
disease 828
organizing phase 349, 379–80,381, 587
parainfluenza viruses 192paraquat toxicity 598patchy, discrete 382pathology 349, 380, 380–1polymyositis 826proliferative phase 380–1radiological findings 379respiratory syncytial virus 191rheumatoid arthritis 811, 811SARS 190squamous metaplasia 348systemic lupus erythematosus
815, 816with thrombus 347viral infections 184, 186–7
diffuse alveolar hemorrhageantiphospholipid syndrome
816capillaritis 816clinical features 815–16differential diagnosis 817histopathology 816rheumatoid arthritis 813systemic lupus erythematosus
815–17, 815, 816diffuse idiopathic pulmonary
neuroendocrine cellhyperplasia (DIPNECH)21, 889, 1151, 1173–6
carcinoid tumors 1176clinical features 1173–4gender 1153histopathology 1174–6immunohistochemistry 1174,
1176incidence 1173neuroendocrine cell
proliferation 1177–8reactive 1176
pathology 1174, 1175peribronchiolar fibrosis 1176pulmonary neuroendocrine
cells 1175radiologic features 1173–4,
1174typical carcinoma in situ 1176
diffuse large B-cell lymphoma(DLBCL) 1330–1, 1346
clinical features 1330diagnosis 1330–1immunohistochemistry 1331lymphomatoid granulomatosis
differential diagnosis 1335methotrexate-associated in
rheumatoid arthritis 814molecular pathology 1331pathology 1330, 1330–1primary effusion lymphoma
differential diagnosis1356
pyothorax-associatedlymphoma differentialdiagnosis 1357
diffuse panbronchiolitis (DPB)644, 645
differential diagnosis 644, 646etiology 644laboratory findings 644pathology 644
diffuse parenchymal lung disease366, 366
diffuse pleural fibrosis 1436–7,1444–8, 1447
asbestos fiber counts 1447calcifying fibrous tumor of the
pleura differentialdiagnosis 1430
chest pain 1445–6, 1448clinical manifestations 1445–6differential diagnosis 1447–8drug-induced 1445etiology 1445fungal infections 1447genetics 1444histology 1446–7incidence 1444lag period from asbestos
exposure 1446lung function restriction 1448macroscopic pathology 1446pathophysiology 1448pleural plaque differential
diagnosis 1442pleuropulmonary malignancy
risk 1448progression/prognosis 1448radiographic findings 1446retroperitoneal fibrosis 1445tuberculosis 1447
diffuse pulmonarylymphangiomatosis1258–61
cell of origin 1258classification 1258clinical features 1259clinicopathologic correlation
1259differential diagnosis 1259–60histopathology 1259immunohistochemistry 1259lymphangioleiomyomatosis
differential diagnosis1255
macroscopic pathology 1259,1260
natural history 1260–1prognosis 1260–1radiographic findings 1259treatment 1261
diffuse pulmonarymeningotheliomatosis1228
Dirofilaria (dirofilariasis) 311–14clinical features 311–12coin lesion 312dead parasites 313diagnosis 313epidemiology 311
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life cycle 312organism 311pathology 312–13, 313radiographic features 312subcutaneous 322treatment 314
disseminated intravascularcoagulation (DIC),pulmonary 58
disseminated juvenilexanthogranuloma 126
DNA aneuploidy, squamousdysplasia/carcinoma-in-situ 907
DNA methylation, mesothelialhyperplasia 1454
DNA sequences, mycobacterialinfections 208–9
Doege–Potter syndrome 1431Down syndrome, tracheal
stenosis 69Dressler syndrome 1420drug abuse 596–600cocaine abuse 596–7heroin toxicity 598–9intravenous 599–600lung transplantation lesions
790marijuana abuse 597–8pulmonary artery embolism
684see also intravenous drug
abusedrug-induced lung disease
585–600amiodarone toxicity 590, 590Niemann–Pick diseasedifferential diagnosis 416
nodules 591biopsy 585–6bleomycin toxicity 591–2busulfan toxicity 591, 592chronic interstitial
pneumonitis 587–8diagnosis 585diagnostic criteria 585diffuse alveolar damage
586–7, 589diffuse pleural fibrosis 1445eosinophilic pneumonia 588filler substance histologic
characteristics 599granulomatous inflammation
589granulomatous pneumonitis 465histologic pattern 585–90infliximab toxicity 593, 593interstitial in hypersensitivity
pneumonitis differentialdiagnosis 465
KL-6 levels 585lung transplantation 790lymphomatoid granulomatosis
1332lupus 589–90, 819, 1426–7
methotrexate toxicity590–1,591drug-induced lymphoma814, 1345
monoclonal antibody toxicity592–3
nitrofurantoin toxicity 592nonspecific interstitial
pneumonia 587–8organizing pneumonia 588pathogenesis 586patterns of injury 587pleural disease 589–90, 1412,
1426–7plexogenic arteriopathy 673pulmonary alveolar
proteinosis 589pulmonary edema 589pulmonary hemorrhage 589, 742pulmonary hypertension 589rapamycin/rapamycin analog
toxicity 592sirolimus toxicity 592, 791, 1255systemic lupus erythematosus
819tyrosine kinase inhibitor
toxicity 592, 593usual interstitial pneumonia
587–8vasculitis 589veno-occlusive disease 589
drug reactions, sarcoidosisdifferential diagnosis 492
dysplasia see squamous dysplasia/carcinoma-in-situ(SD/CIS)
Duffy blood group 297dyspneadiffuse pleural fibrosis 1445pleural effusion 1410solitary fibrous tumor of the
pleura 1435dystrophic ossification 54
E-cadherin 1495mesothelioma diagnosis 1499sarcomatoid mesothelioma
1503echinocandins 239, 244echinococcosis 328–34Echinococcus granulosus hydatid
lung disease 328–31alveolar 332antibody detection 330clinical features 328–9cytology 331diagnosis 330–1differential diagnosis 330–1epidemiology 328hooklets 332hydatid cyst 328–34, 330, 331immunodiagnostic tests 330life cycle 329organism 328pathology 329–30protoscolices 331
radiographic appearance 330Echinococcus multilocularis
hydatid lung disease 332–3clinical features 332diagnosis 332epidemiology 332organism 332pathology 332treatment 332–3
echinoderm microtubule-associated protein-like4–anaplastic lymphomareceptor tyrosine kinasesee EML4-ALK fusion gene
echovirus 118Ecstasy abuse 600ectopic pulmonary deciduosis
876, 877, 878ectopic tissue in lungs 90–1, 91efferent autonomic nerves 12EGFR gene mutations
see endothelial growthfactor receptor (EGFR)gene mutations
Ehlers–Danlos syndrome 429–32classification 430clinical features 430epidemiology 429genetics 430laboratory findings 431parenchymal tears 430–1pathology 430–1, 431pathophysiology 431pleural fibrosis 1445primary spontaneous
pneumothorax 1415prognosis 431radiological findings 430, 430treatment 431–2vascular type 430, 431
Ehrlichia chaffeensis pneumonia179
Eisenmenger’s syndrome,plexogenic arteriopathy673
elastic fibers, pigmentation 58elastic recoil, aging effects 32elastin, absence in pulmonary
hypoplasia 93electron microscopy (EM) 50embolism 112EML4-ALK fusion gene 1191translocation in lung
adenocarcinoma 1063,1066
Emmonsia parvasee adiaspiromycosis
emphysemaA1AT deficiency 619–20adaptive immune response 621alveolar septal fibrosis 386bullous 615, 618centriacinar 615, 617centrilobular 616classification 615, 615–18, 616
congenital lobar 85–6, 85, 86definition 614development-related airspace
enlargement 623focal 615genetics 607homeostatic maintenance/
repair system disruption620–1
idiopathic pulmonary fibrosis608
immunological process 621irregular 615–18, 619localized giant bullous 624–5lung destruction 609lymphangioleiomyomatosis
1254, 1255macrophages 620Marfan syndrome 428methylphenidate abuse 600neutrophils 620non-destructive 623oxidant damage 620panacinar 615, 617paraseptal 615, 618pathogenesis 620–1placental transmogrification
626–7, 626proteolytic/antiproteolytic
imbalance 620pulmonary interstitial 109–11,
110radiological findings 608repair response after injury
620–1senile lung 623smoking 620, 621starvation 623–4vascular endothelial growth
factor function 620see also chronic obstructive
pulmonary disease(COPD)
empyema 1412, 1425Encephalitozoon
(microsporidiosis) 304,305, 305
Encephalitozoon cuniculi(microsporidiosis) 233,304, 304–5
clinical features 304–5differential diagnosis 305epidemiology 304organism 304pathology 305treatment 305ulcerative tracheitis 305
encephalomyelitis, lung cancer973–4
endobronchial metastases 1384–9diagnosis 1388–9gross pathology 1386histology 1386radiographic findings 1386treatment 1386–8
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endocrinologic syndromes, lungcancer 972
endometrial carcinoma 1377metastases 1386, 1398
endometrial sarcoma, metastases1387
endometrial stromal sarcoma,metastases 1381, 1398
endometriosisperitoneal 1525pleural 1427–8, 1428
endometriosis, pulmonary 875–9clinical features 875clinopathological correlation
878cytology 877–8differential diagnosis 878, 878–9ectopic pulmonary deciduosis
876epidemiology 875etiology 875histopathology 875–6, 876, 877immunohistochemistry 878macroscopic pathology 875, 876natural history 879nodules 875, 876pathogenesis 878prognosis 879radiographic features 875, 875,
876treatment 879
endosalpingiosis 1525, 1525–6endothelial cellsactivation 353, 354–5acute lung injury 354–5, 355development 5
endothelial growth factorreceptor (EGFR)
atypical adenomatoushyperplasia 923–4
pulmonary adenocarcinoma 50pulmonary preinvasive
disease 905endothelial growth factor
receptor (EGFR) genemutation 924–5
lung adenocarcinoma 1062,1066
mesothelioma 1466mucoepidermoid carcinoma
1131pleomorphic carcinoma 1190–1pulmonary
adenocarcinogenesis 924endothelial growth factor
receptor (EGFR) genemutations 924, 924–5
endothelial growth factor receptor(EGFR) signaling pathway1062–3
endothelial growth factorreceptor (EGFR) tyrosinekinase inhibitors 1062
endothelins, pulmonaryhypertension 392
Entamoeba gingivalis 293–4Entamoeba histolytica
(amebiasis) 291–4, 292clinical features 293diagnosis 293differential diagnosis 293–4epidemiology 291–2organism 292–3pathology 293pleuropulmonary patterns 293treatment 294
enteric adenocarcinoma 1077–9enteric cysts 88–9Enterobacteriaceae, pneumonia
175–6Enterobius vermicularis
(enterobiasis) 320, 321Enterococcus pneumonia 176Enterocytozoon (microsporidiosis)
304, 305enterovirus 118environmental irradiation,
squamous dysplasia/carcinoma-in-situ 892
environmental pollutionasbestos 515, 1437–8, 1460chrysotile 1437, 1438erionite 1459lung cancer 951–2tremolite 1437–8, 1459, 1459–60
eosinophil(s)asthma 566chronic eosinophilic
pneumonia 569–70Churg–Strauss syndrome 734
eosinophilic bronchiolitis 644eosinophilic lung disease 563–80acute eosinophilic pneumonia
577–80allergic bronchopulmonary
fungal disease 573–5non-asthmatic eosinophilic
bronchitis 568see also asthma, chronic
eosinophilic pneumonia(CEP)
eosinophilic pleuritis 1352eosinophilic pneumoniaacute 588drug-induced lung disease 588rheumatoid arthritis 588, 814see also chronic eosinophilic
pneumonia (CEP)eosinophilic pneumonitisdesquamative interstitial
pneumonia differentialdiagnosis 389
toxocariasis 319eosinophilic vasculitis,
pneumothorax differentialdiagnosis 1419
eotaxin 1412epidermal lysosomes, squamous
cell carcinoma 1103epithelial cell(s), CFTR 98
epithelial cell balls, asthma 567epithelial hyperplasia,
pre-invasive change 892epithelial membrane antigen
(EMA) 1430, 1489, 1494mesothelial hyperplasia 1453mesothelioma 1499, 1504–5
epithelial stem cells 7epithelial–mesenchymal
transition (EMT),sarcomatoid carcinoma1186–7
epithelial–myoepithelialcarcinoma 1136–8, 1136
cell of origin 1136classification 1136clinical features 1136clinicopathologic correlation
1138cytology 1136–7, 1137differential diagnosis 1138electron microscopy 1137genetics 1136histopathology 1136immunohistochemistry 1137,
1137macroscopic pathology 1136molecular findings 1138myoepithelial cells 1136–7natural history 1138pneumocytic
adenomyoepitheliomadifferential diagnosis1145
prognosis 1138radiographic findings 1136
epithelioid cells, sarcoidosis 489epithelioid
hemangioendothelioma(EHE) 1263–8, 1265, 1514
cell of origin 1263–4classification 1263–4clinical features 1264, 1513clinicopathologic correlation
1264–6cytology 1264definition 1513diagnosis 1265–6differential diagnosis 879,
1266–7, 1435, 1513–4electron microscopy 1264histology 1513histopathology 1264immunohistochemistry 1264Kaposi’s sarcoma differential
diagnosis 1513–4macroscopic pathology 1264mesothelioma differential
diagnosis 1513–4molecular findings 1264natural history 1268nodules 1264prognosis 1268pulmonary endometriosis
differential diagnosis 879
radiographic findings 1264solitary fibrous tumor of the
pleura differentialdiagnosis 1435
treatment 1268epituberculosis, childhood 218Epstein–Barr virus (EBV) 198–9,
368cytotoxic drug-induced
lymphoma 1345endobronchial leiomyomatous
polyp 789inflammatory myofibroblastic
tumor 1275lung cancer 956lung transplantation 789lymphoepithelioma-like
carcinoma association1120
lymphoid interstitialpneumonia 1320
lymphomatoid granulomatosis199, 1334
lymphoproliferative disorders814
neoplasms 789NK/T-cell lymphoma, nasal
type 1335pneumonia 198–9, 200post-transplant
lymphoproliferativedisease 778, 786–9,1345
pulmonarylymphoepithelioma-likecarcinomas 956
pyothorax-associatedlymphoma 1356
Epstein–Barr virus (EBV)-associated B-celllymphoproliferativedisorders 1344
Erdheim–Chester disease 1353,1354, 1521
clinical features 1353Gaucher disease differential
diagnosis 412pathology 1353–4pleural 1522
erionite 538–9, 1459, 1459, 1461erlotinib 1066EGFR mutations 1062toxicity 593
Escherichia coli pneumonia 150,160, 175
esophageal atresia,tracheoesophagealfistula 70
esophageal development 4esophageal dysmotility, connective
tissue disease 804estrogen receptor(s) (ER)atypical adenomatous
hyperplasia 925lung adenocarcinoma 1066
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estrogen receptor b,mesothelioma 1529
eukaryotic initiation factor 4E 925Ewing’s sarcoma 124, 124,
1376–7, 1519–20diagnosis 124
ex vivo lung perfusion (EVLP),lung transplantation 795
exogenous lipid pneumonia 632extra-corporeal membrane
oxygenation (ECMO),complications 111
extrapleural pneumonectomy,mesothelioma prognosisafter 1530
extremely-low gestational age,bronchopulmonarydysplasia 6
extrinsic allergic alveolitissee hypersensitivitypneumonitis
Fabry cells 413Fabry disease 417–18clinical manifestations 417cytology 418diagnosis 418electron microscopy 418, 418epidemiology 417genetics 417laboratory findings 418natural history 418pathology 417–18, 418pathophysiology 418prognosis 418radiological findings 417
factor V Leiden mutation 679–80Fallot’s tetralogy, tracheal
stenosis 68familial adenomatous polyposis
(FAP), sclerosinghemangioma association865
familial cryptogenic fibrosingpleuritis with Fanconi’ssyndrome 1445
familial Mediterranean fever,peritoneal mesothelioma1461
Fanconi’s syndromearteriovenous malformations
1261familial cryptogenic fibrosing
pleuritis 1445Farber bodies 426Farber disease 426–7clinical features 426electron microscopy 426epidemiology 426genetics 426laboratory findings 426pathology 426pathophysiology 426prognosis 426–7treatment 426–7
farmer’s lung 441, 442, 446, 467Fasciola hepatica (fascioliasis)
328FBN1 gene mutations 428feeding vessel sign 150–1ferruginous bodies, non-asbestos
518fetal adenocarcinoma 1073–7,
1170blastoma, differential diagnosis
1204carcinosarcoma differential
diagnosis 1204clinical features 1073cytology 1074differential diagnosis 1074,
1077electron microscopy 1077high-grade lesions 1073–8immunohistochemistry 1074–6low-grade lesions 1073, 1074morules 1074–6pathology 1073, 1074pleomorphic carcinoma
differential diagnosis1192
radiography 1074treatment 1077
fetal breathing impairment,pulmonary hypoplasia 91
fetal distress, meconium aspiratesyndrome 113
FHIT (fragile histidine triad) 906,1465–6
fibrillin-1 428, 429, 621fibroblast growth factor (FGF)
5, 5–6fibroblast growth factor 10
(FGF-10) 6fibroblast growth factor receptor
(FGFR) geneabnormalities 68
fibroepithelial polypssee bronchialinflammatory polyps
fibrohistiocytic neoplasms 1273–5fibrosarcoma, ameloblastic 1394fibrous glass 550fibrous webs, tracheal 71filarial infections 308–14clinical features 309diagnosis 310–11epidemiology 308organism 308–9pathogenesis 311pathology 309–10
fine-needle aspiration (FNA)41–2, 977
fissures 8fixationlarge specimens 46–7research techniques 47wedge biopsy 44–5
flavonoids, lung cancerprotection 959
fluconazole, Candida infectiontreatment 268
fluoro-edenite 1461folate 959–60folded lung 1436–7, 1448–51clinical manifestations 1448–9cytology 1450differential diagnosis 1451etiology 1449histopathology 1450–1macroscopic pathology 1450non-asbestos causes 1449prognosis 1451radiology 1449–50
follicular bronchiolitis 644, 646,810, 1318–9, 1319
benign pulmonary lymphoidproliferations 1318
clinical features 1318–9lymphoid hyperplasia 1318pathology 646, 1319prognosis 1319radiological features 1319rheumatoid arthritis 812–13
follicular dendritic cell sarcoma1352, 1352
follicular lymphoma 1331food flavorer’s lung disease 553foods, component effects on cell
function 959foreign bodygiant cell reaction 52–3, 686granulomas in sarcoidosis
differential diagnosis 492pulmonary embolism 686
foreign body-type cells fromaspiration, tuberculosisdifferential diagnosis 222
formalin fixation, wedge biopsy 45formalin inflation of lobes 46FOX genes, alveolar capillary
dysplasia 90fragile histidine triad (FHIT)
906, 1465–6Francisella tularensis 170pneumonia 170, 178
Fraser’s syndrome 87, 92frozen section 44–5wedge biopsy 44
Fryns syndrome, diaphragmatichernia 94
function of lungs 13–17fungal infections 226–78broncholithiasis 635diffuse pleural fibrosis 1447epidemiology 226–8histologic features 227HIV infection opportunist
infections 228incidence 227–8inflammatory myofibroblastic
tumor 1275lung carcinoma 957lung transplantation 774, 785organisms 226
pneumonia 147pulmonary hyalinizing
granuloma differentialdiagnosis 874
risk factors 227superinfection on viral
infections 185tuberculosis differential
diagnosis 221underlying diseases 227see also named infections and
organismsfungus balls 229, 232Scedosporium infection 243see also aspergilloma
Fusarium infection (fusariosis)243–4, 244
Aspergillus differentialdiagnosis 238
chlamydoconidia 244clinical features 244diagnosis 244epidemiology 243–4incidence 228organism 243pathology 244prognosis/treatment 244
galactocerebrosidasegalactosylceramideb-galactosidase 423
a-galactosidase A 417, 418GALC gene mutations 423ganglioneuroma 1519gastric adenocarcinoma,
metastases 1390gastrin-releasing peptide (GRP)
1165gastroesophageal reflux disease
(GERD) 466gastrointestinal autonomic nerve
tumor (GANT) 1511–2gastrointestinal pseudo-
obstruction 974gastrointestinal stromal tumor
(GIST) 1237metastases 1396–7, 1396solitary fibrous tumor of the
pleura differentialdiagnosis 1435
Gaucher cells 410–11, 411, 413,412, 700
conditions mimicking 412cytology 411electron microscopy 411
Gaucher disease 409–14, 700clinical manifestations 409–10cytology 410, 411, 411differential diagnosis 412–13enzyme replacement therapy
413–14epidemiology 409, 410genetics 409interstitial lung disease 410laboratory findings 411
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Gaucher disease (cont.)natural history 413–14pathology 410–11, 411pathophysiology 411–12prognosis 413–14pulmonary hypertension
410, 412, 698enzyme replacementtherapy 414
radiological findings 410type 1 409, 410, 410, 412type 2 409, 410type 3 409, 410
Gaucher-like cells, GM1gangliosidosis 423
GCDFP-15, lungadenocarcinoma 1066
gefitinib 1062, 1066genomic instability, pulmonary
preinvasive disease907–8
Geotrichum capitatum infection228
gestational trophoblastic disease,metastases 1398–9
giant cell arteritis 745–7cellular immunity 746clinical manifestations 746differential diagnosis 747disseminated visceral 747epidemiology 745genetics 746histopathology 746humoral immunity 746infections 746laboratory findings 746natural history 747pathogenesis 746pathology 746prognosis 747Takayasu arteritis differential
diagnosis 747, 747, 748giant cell carcinoma 1196giant cell pneumonia 193giant cell sarcoma 1195–7clinical features 1196cytology 1197definition 1195–6differential diagnosis 1197electron microscopy 1197histopathology 1196–7immunohistochemistry 1197inflammatory stroma 1196–7macroscopic pathology 1196natural history 1197prognosis 1197smoking 1196
giant cell tumor 1197, 1275, 1276,1376–7
glandular inclusions, benign 1393glandular papilloma 856, 1065mixed squamous cell
papilloma 856, 857glass fiber 550glial tissue, ectopic 91
glioblastoma multiforme,metastases 1387
globoid leukodystrophysee Krabbe disease
glomangiosarcoma 1248, 1249Glomeromycota infection 228glomus tumors see primary
pulmonary glomus tumors‘gloved finger’ sign, allergic
bronchopulmonaryfungal disease 574
glucocerebrosidase genemutations 409
GLUT1 glucose transporter,mesothelioma diagnosis1500
glutathione-S-transferase (GST)950, 951
gene polymorphisms 519, 891,1440
glycogen storage disease, type II425–6
glycosaminoglycans 421, 422, 423glycosphingolipid 417–18GM1 gangliosidosis 423clinical manifestations 423natural history 423pathology 423, 424prognosis 423
Gnathostoma spinigerum(gnathostomiasis) 321–2
goblet cells 15, 18hyperplasia 892, 892metaplasia 565
Goodpasture syndrome 736–40acute interstitial pneumonia
differential diagnosis 382ANCA 739anti-basement membrane
antibodies 738, 739autoantibodies 739clinical manifestations 736–7cytology 737differential diagnosis 740epidemiology 736genetics 736hemoptysis 736–7hemosiderin-laden
macrophages 737immunohistochemistry 738, 739laboratory findings 738natural history 740pathogenesis 739–40pathology 737, 738prognosis 740pulmonary endometriosis
differential diagnosis 879radiographic findings 737, 737relapse rates 740ultrastructural studies 737Wegener’s granulomatosis
overlap 739–40Gorham–Stout syndrome
1428–9Gottron’s papules 825
Gram-negative bacteria,pneumonia 148
granular cell tumors 1239–42cell of origin 1240classification 1240clinical features 1240clinicopathologic correlation
1242cytology 1242differential diagnosis 1242electron microscopy 1242histopathology 1241, 1241–2immunohistochemistry 1242macroscopic pathology 1240–1,
1241malignancy 1242molecular findings 1242multiple endobronchial 1240–1natural history 1242prognosis 1242radiographic findings 1240, 1240
granulation tissue, Kaposi’ssarcoma differentialdiagnosis 1272
granulocyte–macrophagecolony-stimulating factor(GM-CSF)
Langerhans cell histiocytosis1351
lung cancer 975pulmonary alveolar
proteinosis 395, 397granulocytic sarcoma 1347granulocytosis 975granulomasallergic in Churg–Strauss
syndrome 734, 735hyalinizing 1430infectious 729necrotising 219pleural calcified 1430tuberculous type 218–19see also sarcoid granulomas
granulomatous disorders 464–7pleural disease 1423–5see also bronchiolitis,
granulomatous,bronchocentricgranulomatosis,necrotizing sarcoidgranulomatosis,pulmonary hyalinizinggranuloma (PHG),Wegener’s granulomatosis
granulomatous inflammation222, 589
Wegener granulomatosis724–5, 726–7, 728
granulomatous lymphadenitis 635granulomatous pleural disease
1423–5granulomatous pneumonitis
465, 466granulosa cell tumors of ovary,
metastases 1398
graphite miners’ lungs 536Grimelius technique 1164gross cystic disease fluid protein
(GCDFP-15), lungadenocarcinoma 1066
ground-glass nodules (GGN),lung adenocarcinoma1048–9, 1048
Group B streptococcal infection115
hyaline membrane disease105, 105
pneumonia 115–16growth factors 5, 1466–7growth of lungpulmonary neuroendocrine
cells 20sex effect 6stages 1trachea 6
H1N1 influenza 182, 184acute bronchiolitis 640antigenic shift 187infection spread 188pandemic 184pathology 190risk factors 188
Haemophilus influenzae 160, 161cystic fibrosis 99pleural exudate 160pneumonia 147, 176
halo signhemorrhage in metastases 1378invasive aspergillosis 235, 244reversed in mucormycosis 240
Hamazaki–Wesenberg bodies59, 59
sarcoidosis 486, 486Hamman–Rich syndrome
see acute interstitialpneumonia (AIP)
Hand–Schüller–Christian disease1348
Hantavirus 182hemorrhagic fever 199
hantavirus pulmonary syndrome199–200, 200
hard metal lung disease 541–3clinical presentation 542cytology 542diagnosis 542–3differential diagnosis 543giant cell interstitial
pneumonitis 543pathogenesis 542pathology 543, 544radiographic findings 542susceptibility 542
Harlequin sign 970, 970hASH1 transcription factor 1165HBME-1 1499, 1503head and neck cancer 946, 1393metastases 1393, 1394
heart, development 4
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heat-shock proteins (Hsp) 751, 906Hecht’s giant cell pneumonia 193hedgehog interacting protein
957helminths 288, 308–35cestodes 328–35filarial infections 308–14nematodes 308–22pulmonary eosinophilia
syndromes 308soil-transmitted 314–18trematodes 322–8
hemangioendotheliomasee epithelioidhemangioendothelioma
hemangiomas 1263, 1263differential diagnosis 1263pathology 1263
hematite 543–4hematite miner’s lung 543–4complications 544
hematologic syndromes, lungcarcinoma 972, 975
hemoptysisBehçet syndrome 750Goodpasture syndrome 736–7pulmonary endometriosis 875
hemorrhagic fever, Hantavirus199
hemosiderin, biopsy artefact 51–2hemosiderosis see idiopathic
pulmonaryhemosiderosis
Hennekam syndrome 87hepatic cirrhosis, pleural effusion
1411hepatitis C virus, primary
effusion lymphoma 1355hepatocellular carcinoma,
metastases 1395–6hepatocyte growth factor,
mesothelioma 1467HER2 gene 905, 924hereditary hemorrhagic
telangiectasia,arteriovenousmalformations 1261, 1262
Hering Breuer reflex 1436Hermansky–Pudlak syndrome
418–21ceroid storage 421clinical manifestations 419cytology 420, 421differential diagnosis 421electron microscopy 421, 421epidemiology 418–19genetics 419natural history 421pathology 419–21, 419, 420pathophysiology 421prognosis 421pulmonary fibrosis 419, 421radiological findings 419, 419
heroin toxicity 598–9pathology 598–9
herpesvirus (HSV) 117, 184,195–7, 197
ARDS 196bronchiolitis 186diagnosis 196, 197, 198immunocompromised
patients 198immunosuppression 196–7inclusions in squamous
respiratory epithelium199
lung transplantation 784–5neutrophilic exudate 197pneumonia 117, 196polykaryons with nuclear
inclusions 197radiographic appearance 196respiratory mucosa 196see also Epstein–Barr virus
(EBV), varicella zostervirus (VZV)
high-frequency jet ventilation(HFJV), complications 111
high-resolution computedtomography (HRCT),lung carcinoma 965
hilar lymph nodescystic fibrosis 103metastatic pulmonary nodular
disease 1393hilar lymphadenopathy 1393histiocytic disorders 1354crystal-storing histiocytosis
412, 413see also Langerhans’ cell
histiocytosishistiocytic sarcoma 1352histiocytosiscrystal-storing 1341Erdheim–Chester disease
1354Rosai-Dorfman disease 1354
histiocytosis X 1348histochemical stains 49histological processinglarge specimen 43–5small specimen 42–3
histology of lungs 13–17Histoplasma capsulatum
var. capsulatum(histoplasmosis) 228,245–50, 245
acute disease 245–6, 247antigen detection test 249Candida differential diagnosis
267–8chronic cavitary 246, 246, 247cicatricial 246, 247clinical features 245–6coccidioidomycosis differential
diagnosis 262complement fixation test 249culture 247–8diagnosis 247–50differential diagnosis 249–50
epidemiology 245folded lung differential
diagnosis 1451forms 245, 246immunodiffusion test 249latent disease 246latex agglutination test 249leishmania differential
diagnosis 290–1lymphomatoid granulomatosis
differential diagnosis1336
organism 245pathogenesis 245pathology 246–7PCP differential diagnosis 272progressive disseminated
246–7, 248serological tests 248–9South American blastomycosis
differential diagnosis 264toxoplasmosis differential
diagnosis 303treatment 250
Histoplasma capsulatum var.duboisii (Africanhistoplasmosis) 249–50
HIV/AIDS-related lymphoma1344
HIV infection 200–2amebiasis 294BMPR2 expression inhibition
670Candida infection 265cavitary rheumatoid nodules
807CMV infection 195, 196cryptococcosis 254Kaposi sarcoma 1268, 1272leishmaniasis 290lung cancer 956lymphoid interstitial
pneumonia 264, 1319,1320
lymphomatoid granulomatosis1332
microsporidiosis 304nonspecific interstitial
pneumonia 266opportunistic infections 182,
228Pneumocystis jiroveci
pneumonia 268, 269primary effusion lymphoma
1355pulmonary abnormalities 201sarcoidosis 490South American blastomycosis
263tuberculosis coinfection 206,
209, 211, 223virus 262
HMB-45 immunostain,lymphangioleiomyomatosis 1253
Hodgkin lymphoma 1342, 1347clinical features 1342cytology 1342differential diagnosis 1342lymphocyte predominant 1347lymphomatoid granulomatosis
differential diagnosis1335
pathology 1342, 1342primary effusion lymphoma
differential diagnosis1356
pyothorax-associatedlymphoma differentialdiagnosis 1357
hookworm infection 316, 316horseshoe lung 75, 75host defensebacterial infections 153barriers 153foreign material recognition 153pneumonia 152–4
hot-tub lung 211, 219–20, 220,458–9
granulomas 458–9, 458histopathology 458–9presentation 458radiological findings 458treatment 459
HPS gene mutations 419Hughes–Stovin syndrome 751–2,
832b-human chorionic
gonadotrophin (b-hCG),pleomorphic carcinoma1190
human herpes virus 6 (HHV-6)199, 784, 1351
oncogenesis mechanism 1271–2human herpes virus 7 (HHV-7)
784human herpes virus 8 (HHV-8)
1268detection 1271inflammatory myofibroblastic
tumor 1275latent infection 1272primary effusion lymphoma
1355human metapneumovirus 191human milk fat globulins
(HMFG), mesothelioma1499
human papilloma virus (HPV)lung cancer 953–6squamous cell carcinoma 906,
1098–9squamous cell papillomas
850, 852–3, 855transmission route 956
human T cell lymphotropic virus1 (HTLV-1) 316, 644
humoral factors, viral infections184
humoral immunity 735, 746
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Hunter syndrome 421, 422Hurler syndrome 421, 422Hurler–Scheie syndrome 422hyaline membrane disease
103–6, 104, 107bronchopulmonary dysplasia
106epithelial–endothelial injury
105–6, 105Group B streptococcal
infection 105, 105ischemia 105–6prematurity-associated 105–6term presentation 105–6thyroid transcription factor 1
1016ventilatory therapy 106see also respiratory distress
syndromehyaline membranesacute eosinophilic pneumonia
579acute lung infection/ARDS
345–6, 347diffuse alveolar damage 186
hyalinizing granuloma 1430hydatid cyst 328–34, 330, 331degenerate 331see also Echinococcus granulosus
hydatid lung diseasehydatid lung disease
see Echinococcusgranulosus hydatid lungdisease, Echinococcusmultilocularis hydatidlung disease
hydatiform mole, invasive 1399hydrocele, benign reactive
mesothelial proliferations1472–3
hydrops fetalis, congenitalperibronchialmyofibroblastic tumor 124
5-hydroxytryptamine (5-HT)see serotonin
hyperacute rejection, lungtransplantation 768,771–2, 773
hypercalcemia, paraneoplasticsyndrome in lungcancer 971
hyperinfection syndrome,strongyloidiasis 317
hyperinflation of lungs 623hypersensitivity pneumonitis
367, 371, 439–67acute 443, 450acute exacerbations 441, 458airspace organization 453antigens 441, 442, 446avoidance 467
aspergillosis 230bronchiolitis 450, 455bronchiolitis obliterans
organizing pneumonia 455
bronchoalveolar lavage 442–3carbon monoxide diffusion
capacity 442centrilobular fibrosis 455–7chronic 442, 443, 454, 455, 456,
457, 458acute exacerbations 458immunological pathways 449Japanese summer-type 459pathological findings 454–8radiological findings 444–6
classification 439, 440clinical features 439–43clinical testing 441–3consort 441diagnostic criteria 439differential diagnosis 459–67,
460early/subacute 450, 451etiology 446–9, 447fibrosis 455–7, 457honeycomb 457
fibrotic 441, 445–6forms 458–9gene analysis 446–9gene expression patterns 449granulomas 451–3, 454hot tub lung 458–9
ground-glass opacification443–444, 444, 445, 446
hard metal lung diseasedifferential diagnosis 543
immunological pathways446–9
immunological testing 442incidence 439–41inciting agents 446inflammatory pathway 449inhalational challenge 443interstitial lung disease 441interstitial pneumonitis 451,
455intraluminal fibrosis 453, 455isocyanate-related 459Japanese summer-type 459lymphangioleiomyomatosis
differential diagnosis1255
lymphoid proliferation 1318metal-working fluids 459, 467microchimerism 449mucostasis 454neutrophilia 443nonspecific interstitial
pneumonia pattern 378pathogenesis 446–9pathological findings 449–58,
453, 1318pathophysiology 441–2prevalence 439–41prognosis 467provocation tests 443pulmonary function testing
441–2radiological findings 443–6
sarcoidosis differential diagnosis491
skin testing 443smoking effects 449subacute 443, 451, 452, 453immunological pathways449
pathological findings 450–3phase 442radiological findings 443–4
subacute/chronic 451, 452survival 467treatment 467vasculopathy 457–8
hypersensitivity-type disease219–20
hypertrophic pulmonaryosteoarthropathy(HPOA) 973
solitary fibrous tumor of thepleura 1431
hypoglycemia, paraneoplastic1431
hyponatremia of malignancy972
hypoxemic hepatopulmonarysyndrome 325
hypoxiasickle cell disease 680
hypoxic arteriopathy 686–9, 690associated conditions 689causal factors 686–9COPD 688epidemiology 686–9histopathology 689intimal fibrosis 689medial hyperplasia 689pulmonary artery adventitial
thickening 689vascular lesions 689
idiopathic crescenticglomerulonephritis,autoantibodies 711
idiopathic interstitial pneumonia366, 464, 806
idiopathic lymphocytic pleuritis(ILP) 1449
idiopathic mediastinal fibrosis1447–8
idiopathic pleuroparenchymalfibroelastosis 390–1, 1423
idiopathic pulmonary arterialhypertension (IPAH),lung transplantation 768
pediatric 768idiopathic pulmonary fibrosis
(IPF)acute exacerbation 383–5clinical presentation 383diagnostic criteria 383differential diagnosis 384natural history 385pathogenesis 384pathology 383, 384
prognosis 385progression 384radiological changes 383
endothelin-1 392hypersensitivity pneumonitis
differential diagnosis 449lung cancer association 957–8malignancy association 372pathology 369, 370pulmonary hypertension 392usual interstitial pneumonia
pattern 371, 372see also usual interstitial
pneumonia (UIP)idiopathic pulmonary
hemosiderosis 742, 743,879
illicit drug abuse 596–600cocaine abuse 596–7heroin toxicity 598–9intravenous 599–600lung transplantation lesions
790marijuana abuse 597–8
imatinib 593immune anatomy 185immune complex deposition,
systemic lupuserythematosus 817
immune dysfunction, silicosis531–2
immune reconstitutioninflammatory syndrome(IRIS) 490
immune responseCandida infection 264histoplasmosis infection 245innate 154
immunocompromised patientsacute bronchiolitis 640acute bronchopneumonia 150adenovirus 193amebiasis 294Aspergillus infection 229babesiosis 300blastomycosis 199Candida infection 265coccidioidomycosis 260,
261, 262cryptococcosis 251–2cytotoxic drug-induced
lymphoma 1345herpesvirus 198histoplasmosis 245–6HIV/AIDS-related lymphoma
1344influenza severity 189lymphoma in congenital
immunodeficiency 1344lymphomatoid granulomatosis
1332malignant lymphoma 1344microsporidiosis 304Pneumocystis jiroveci
pneumonia (PCP) 268–9
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Scedosporium infection 243South American blastomycosis
263sporotrichosis 272strongyloidiasis 316toxoplasmosis 303see also HIV infection,
post-transplantlymphoproliferativedisease (PTLD)
immunodeficiency, congenital 1344immunoglobulin A (IgA) 644immunoglobulin A, secretory
(sIgA) 184immunoglobulin (Ig) deposition
disease 1340immunoglobulin G 4 (IgG4)-
related sclerosing disease1420, 1421, 1520
immunohistochemistry 49–50argentaffinity 1164differential diagnosis problems
1029extra-pulmonary tumors 1030lung tumorscytokeratins 1027diagnosis 1015Napsin A 1023neuroendocrine markers1026, 1027
p16 protein 1027p63 protein 1027rapid technique for frozensections 1023
surfactant protein A 1025,1026
surfactant protein B 1025,1026
see also thyroid transcriptionfactor 1 (TTF1)
immunosuppressionCMV 195diffuse pneumonic
aspergillosis 237HSV infection 196–7iatrogenic 182lung cancer risk 956suppurative aspergillosis 237tracheobronchial aspergillosis
237immunosuppressive drugs, organ
transplantation 1348IMP3 (insulin-like growth
factor II messengerribonucleic acid-bindingprotein 3) 1505
inclusion cysts, peritoneal1522–3, 1523, 1524
infantsneuroendocrine cell hyperplasia
114–15, 641, 1172Pompe disease 425–6preterm 107, 108–9pulmonary alveolar
proteinosis 395
pulmonary vascular anatomy666
see also perinatal lungpathology, persistentpulmonary hypertensionof the newborn
infectionsacute bronchiolitis 638–9, 640acute cellular rejection
morphological mimics 777acute interstitial pneumonia
differential diagnosis 382acute lung injury/ARDS 350,
357trigger 343
amniotic fluid 115ascending 115Behçet’s syndrome 751bronchiolitis 638–9, 640, 151chronic bronchitis in COPD 612cystic fibrosis 99–100fetal 115folded lung differential
diagnosis 1451giant cell arteritis 746granulomatous bronchiolitis
645–6immunohistochemistry 49lung cancer 953–7lung transplantation 770, 774,
783, 783–9community-acquired 783early complications 773–4
lymphomatoid granulomatosisdifferential diagnosis1336
MALT lymphomas 1324mid-trimester miscarriage 115middle lobe syndrome 633–4nosocomial 773–4perinatal 115–18pleural effusions 1412pleural granulomas 1425polyarteritis nodosa 743–4pyoderma gangrenosum
differential diagnosis 832–3risk in Wegener
granulomatosis 715sarcoidosis 477, 488, 491scarring from healed
infection 54sickle cell disease 680Wegener’s granulomatosis
728, 729see also abscess, bacterial
infections, fungalinfections, viral infections
infectious granulomas 729infectious mononucleosis-like
PTLD 787inflammationbronchiectasis 629bronchiolar diseases with/
without adjacentparenchymal disease 643–8
COPD 611cystic fibrosis 99–100granulomatous 222, 589Wegener’s granulomatosis724–5, 726–7, 728
IL-6 670lung cancer 957pulmonary hypertension 670
inflammation response, COPD623
inflammatory bowel disease833–5
ANCAs 834–5clinopathological patterns 834differential diagnosis 834–5prognosis 835
inflammatory cascade,bronchopulmonarydysplasia 108–9
inflammatory cells, acute cellularrejection morphologicalmimic 777
inflammatory myofibroblastictumor (IMT) 118–19,125–6, 1275–8, 1520–1
ALK gene association 1277calcifying fibrous tumor of the
pleura differentialdiagnosis 1430
cell of origin 1276classification 1276clinical features 1277clinicopathologic correlation
1277–8cytology 1277differential diagnosis 1278electron microscopy 1277etiology 1275histopathology 1277immunohistochemistry 1277macroscopic pathology 1277molecular findings 1277natural history 1278pleomorphic carcinoma
differential diagnosis1194
pleural 1521prognosis 1278pulmonary hyalinizing
granuloma differentialdiagnosis 874
radiographic findings 1277spindle cell carcinoma
differential diagnosis1194
inflammatory polypsetiology 847pathology 848, 849radiological findings 848squamous cell papilloma
differential diagnosis 855inflammatory pseudotumor
1520–1inflammatory response, bacterial
infection 153–4
inflammatory sarcomatoidcarcinoma 1193–4, 1193
infliximab toxicity 593, 593influenzabacterial superinfection 189–90diffuse alveolar damage 189–90pneumonia 186, 189see also H1N1 influenza
influenza A 182–3, 187, 190antigenic drift/shift 187
influenza B 187influenza C 187influenza virus 187–90, 188clinical signs 189diagnosis 189disease severity 189hemagglutinin expression 188infectivity 189neuraminidase expression 188onset 189pandemic outbreak 187–8seasonal 189–90
inhalant abuse 600inhalation pneumonia 149inhaled particles, aerodynamic
equivalent diameter 516inhibitor of apoptosis (IAP)
factors, atypicaladenomatoushyperplasia 923
iniencephalus, lung herniation 75injurylung cancer risk 957–8pulmonary neuroendocrine
cell function 20–1insulin-like growth factor binding
proteins (IGFBP),lymphangioleio-myomatosis 1253
interferon therapy, sarcoidosis490, 492
interleukin 1b (IL-1b) 748interleukin 6 (IL-6) 670, 748, 975interleukin 8 (IL-8) 109interleukin 10 (IL-10) 732intermediate cells 15, 23interstitial emphysema 109–11,
110interstitial fibrosisALI/ARDS 347bronchiolitis 387diffuse 536
interstitial glycogenesis 114interstitial lung disease 113–15,
366–97acute exacerbation of
idiopathic pulmonaryfibrosis 383–5
acute interstitial pneumonia379–83
classification 367, 367connective tissue disease 378dermatomyositis 826desquamative interstitial
pneumonia 367, 388–91
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interstitial lung disease (cont.)diffuse 113–15, 114, 378drug-related 465epidemiology 367–8Gaucher disease 410genetics 368hypersensitivity pneumonitis
441idiopathic pleuroparenchymal
fibroelastosis 390–1lung transplantation 768lymphoid proliferation 1317–8mixed connective tissue
disease 827polymyositis 826prognosis 819pulmonary calcification 392–3pulmonary hypertension 392,
698–700causes 699–700symptoms 699vasculopathy 698–9
pulmonary ossification 392,393
radiographic features 386respiratory bronchiolitis 385–8rheumatoid arthritis 808–9scleroderma 821–2Sjögren’s syndrome 823–4smoking-related 385surgical lung biopsy 366systemic lupus erythematosus
817–19treatment 819undifferentiated connective
tissue disease 829usual interstitial pneumonia/
idiopathic pulmonaryfibrosis 367, 368–74
associated conditions 369histologic features 372
see also diffuse alveolardamage (DAD),non-specific interstitialpneumonia (NSIP),respiratory bronchiolitis-associated interstitial lungdisease (RB-ILD)
interstitial pneumonia 463–4bronchiolocentric 467fibrosing 543chronic 492
see also idiopathic interstitialpneumonia, nonspecificinterstitial pneumonia(NSIP), usual interstitialpneumonia (UIP)
amiodarone toxicity 590drug-induced lung disease587–8
desquamative 114giant cell in hard metal lung
disease 543hypersensitivity pneumonitis
451, 455
intimal fibrosisconcentric laminar 675hypoxic arteriopathy 689plexogenic arteriopathy 674–5pulmonary capillary
hemangiomatosis 693pulmonary hypertension in
systemic sclerosis 697pulmonary veno-occlusive
disease 693intra-alveolar hemorrhagebiopsy artefact 51, 51–2real 52
intra-pulmonary lymph nodes(IPLN) 1316–7, 1317
diagnostic imaging 1316–7metastatic carcinoma 1316silicotic nodules 1316subpleural 12
intra-pulmonary solitary fibroustumor 874
intra-pulmonary thymoma1283–5cell of origin 1284classification 1284clinical features 1284clinicopathologic correlations
1285cytology 1284differential diagnosis 1285genetics 1284histopathology 1284immunohistochemistry 1284macroscopic pathology 1284molecular findings 1284–5natural history 1285prognosis 1285radiographic findings 1284
intrathoracic lymph nodesmetastatic spread 1391–4radiography 1393–4
intravascular large B-celllymphoma 1336, 1337
clinical features 1336differential diagnosis 1337immunohistochemistry 1337molecular pathology 1337pathology 1337plasma cell disorders 1337
intravascular lymphoma 1273intravascular thrombosis 58intravenous drug abuse 599–600filler materials 599, 599pulmonary artery embolism
153, 684ionizing radiation, mesothelioma
1461–2iron-associated disease 543–4, 544iron encrustation 58, 58ischemic heart disease, asbestosis
1437ischemic–reperfusion injury, lung
transplantation 770–1isocyanate-related
hypersensitivitypneumonitis 459
isolated tumor cells (ITCs),lung cancer 1012
Japanese summer-typehypersensitivitypneumonitis 459
juvenile-onset laryngealpapillomatosis 955
juvenile xanthogranuloma,disseminated 126
Kaempferol 959Kampmeier focus 32kaolin macule 538kaolin pneumoconiosis 538pathology 538
kaolinite 538, 1447kaolinosis 1445, 1447Kaposi’s sarcoma 1268–72, 1269cavernous–angiomatous 1271cell of origin 1268classification 1268clinical features 1268clinicopathologic correlation
1272cytology 1271differential diagnosis 1272diffuse pulmonary
lymphangiomatosisdifferential diagnosis1260
electron microscopy 1271epithelioid
hemangioendotheliomadifferential diagnosis1513–4
genetics 1269histopathology 1271HIV infection 1268, 1272immunohistochemistry 1271inflammatory 1271LANA-1 1271, 1272latent infection 1272macroscopic findings 1271molecular findings 1271–2natural history 1272organ transplantation 1268primary effusion lymphoma
1355primary pulmonary
angiosarcoma differentialdiagnosis 1273
prognosis 1272radiographic findings 1269–71spindle cells 1271, 1272treatment 1272
Kartagener’s syndrome 96Katayama syndrome 308, 324keratin genes, squamous cell
carcinoma 1104keratinocyte growth factor,
mesothelioma 1467Ki-67 proliferation index 1505Kirsten-rat derived retroviruses
causing sarcoma
mutations see KRASgene mutations
Klebsiella pneumoniaepneumonia 160, 175
Klippel-Feil syndrome 66, 75Krabbe disease 423–5clinical manifestations 423–4electron microscopy 424, 425macrophages 424pathology 424, 424prognosis 424–5radiological findings 424treatment 424–5
KRAS gene mutations 905atypical adenomatous
hyperplasia 924, 924–5localized non-mucinous
bronchioloalveolarcarcinoma 924
lung adenocarcinoma 924, 924,1062–3, 1068
lung carcinoma 951pleomorphic carcinoma 1190
Krebs von den Lunge-6 (KL-6)glycoprotein 585
Kveim–Siltzbach test, sarcoidosis489
lactate dehydrogenase (LDH)1410, 1529
Lady Windermere’s syndrome219–20, 220, 633–4
Lambert–Eaton syndrome 974,1153
Lambertosis see peribronchiolarmetaplasia
Langerhans cell(s) 1348, 1351Langerhans cell granulomatosis
(LCG) 1419Langerhans cell histiocytosis 1352advanced with pulmonary
hypertension 1351Birbeck granules 1348chronic eosinophilic
pneumonia differentialdiagnosis 573
clinical features 1349clinicopathological
associations 1349cytokines 1351desquamative interstitial
pneumonia differentialdiagnosis 389–90
diagnosis 1349differential diagnosis 1351GM-CSF role 1351HHV-6 association 1351histogenesis 1351immunohistochemistry 49, 1350light chain deposition disease
differential diagnosis 1340lung transplantation 790lymphangioleiomyomatosis
differential diagnosis1255
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malignant 1352multisystem 1352pathology 1350, 1351, 1351prognosis 1349progressive fibrotic 1350pulmonary hypertension 392radiology 1349smoking 1349, 1351treatment 1349
Langerhans cell histiocytosis(LCH) 385
Langerhans cell sarcoma 1352Langerin 1348, 1350lanthanides 544–5large amino acid transporter
type 1 (LAT1) 925large B-cell lymphomaintravascular 1336, 1337see also diffuse large B-cell
lymphoma (DLBCL)large cell carcinoma 1114–21cell of origin 1114classification 1114clinical findings 1114clinicopathologic correlation
1115–6cytology 1115, 1116differential diagnosis 1116–7electron microscopy 1115genetics 1115histopathology 1114–5immunohistochemistry 1115macroscopic pathology 1114,
1115, 1116molecular findings 1115, 1117natural history 1117paraneoplastic syndromes
1114primary pulmonary
angiosarcoma differentialdiagnosis 1273
prognosis 1117radiographic findings 1114,
1115rhabdoid phenotype 1121,
1122, 1242thyroid transcription factor 1
expression 1016, 1019variants 1117–21
large cell neuroendocrinecarcinoma (LCNEC)1019, 1027, 1161
adenocarcinoma component1162
atypical carcinoid tumordifferential diagnosis 1168
basaloid carcinoma differentialdiagnosis 1118
basaloid squamous cellcarcinoma differentialdiagnosis 1107–8
classification 1152clinical features 1153cytology 1161, 1161–2, 1168differential diagnosis 1167
electron microscopy 1166genetics 1166–7histopathology 1160–2immunohistochemistry 1165macroscopic pathology 1155natural history 1169pathology 1156prognosis 1169radiographic findings 1155,
1156small cell lung carcinoma
differential diagnosis1168–9, 1169
large pleural biopsy 49large surgical pathology specimen
processing 43–5, 47–9frozen section 44–5large pleural biopsy 49lung wedge biopsy 43–4surgical techniques 45–7
laryngeal atresia 87, 87laryngotracheobronchitis
see crouplate transforming growth
factor-b binding protein4 (LTBP4) 6
latency-associated nuclear antigen(LANA-1) 1271, 1272
latent TGF-b binding proteins(LTBP) 1467
Legionella, pneumonia 148,149, 176
Legionella micdadei 148, 161, 176Legionella pneumophila 148, 161,
162, 176leiomyoma/leiomyosarcoma
1242–3, 1255, 1382, 1520see also benign metastasizing
leiomyoma (BML)leiomyomatous hamartoma 1256leiomyomatous polyp 789Leishmania (leishmaniasis) 289–91amastigotes 216clinical features 290cutaneous 290diagnosis 290differential diagnosis 290–1epidemic 289epidemiology 289mucocutaneous 289, 290organism 289pathology 290pleural infection 291, 1425respiratory tract 290species 289sporadic 289transmission 289treatment 291visceral 289, 290
lepidic predominantadenocarcinoma (LPA)918, 1044, 1055, 1058–9
leprechaunism, development-related airspaceenlargement 623
Leptospira (leptospirosis)171, 178
Letterer–Siwe disease 1348, 1352leukemia 684–6, 1348, 1401leukotriene receptor antagonists,
Churg–Strauss syndrome735
Lewis antigen 1496Libby mine (Montana, US) 539–40Liebow’s bronchial probe
technique 46–7Li–Fraumeni syndrome 960light chain deposition disease
1340, 1340,differential diagnosis 1340variant 1340
Linguatula pentastomiasis 335lipidaspiration 632in capillaries 112
lipid pneumonia, endogenous/exogenous 412, 416
lipofuscin 418lipoma see primary pulmonary
lipomalipopolysaccharide 1409–10lipopolysaccharide-binding
protein (LBP) 1412liposarcomametastases 1384see also primary pulmonary
liposarcomaListeria monocytogenes 116, 116liver tumors, metastases 1395–6LKB1, atypical adenomatous
hyperplasia 925Loa loa (loiasis) 322lobar agenesis 75lobar consolidation, viral
infections 184lobar emphysema, diagnosis 76–7lobectomysimple 45–7sleeve 46
lobes, formalin inflation 46localized non-mucinous
bronchioloalveolarcarcinoma (LNMBAC)889, 911
atypical adenomatoushyperplasia
differential diagnosis 918distinction 927intermediate features 922mixed cell populations 922transition from 928
cell cycle activity 922collapsed pattern 919Dicer upregulation 927ground-glass opacity 928histologic features 918matrix metalloproteinases 926proliferation index 922
Löffler syndrome 308, 314–15,316, 317, 571
Löfgren syndrome 488, 492Lophomonas 307low-grade adenocarcinoma of the
fetal lung type (L-FLAC)/well-differentiated fetaladenocarcinoma (WDFA)1214
lower respiratory system 7, 14–15,150
lung adenocarcinoma 1043–79acinar subtype 1054age factors 1047apical 970atypical adenomatous
hyperplasia 919–21, 921,926
atypical carcinoid tumordifferential diagnosis1167
BRAF gene mutation 1063breast metastatic
adenocarcinomadifferential diagnosis 1031
bronchial mucosa 909carcinoma markers 1495–6cell of origin 1045central carcinoma 1051, 1051CK5/6 immunohistochemistry
1061classification 1043, 1043–5,
1044clinical features 1047, 1047clinopathologic correlation
1064colloid 1068–73epidemiology 1069immunohistochemistry 1070pathology 1069–70, 1070,1071
prognosis 1070colorectal metastatic
adenocarcinomadifferential diagnosis1031, 1032
copy number alterations1064
CT studies 1049cytokeratins 1028cytology 1056–61, 1060differential diagnosis 1059–61,
1065–6EGFR 50gene mutations 1062, 1066signaling pathway 1062
electron microscopy 1061EML4-ALK translocation
1063, 1066enteric pattern 1077–9, 1079epidemiology 1046–7epithelioid mesothelioma
immunohistochemicaldistinction 1494–5
ethnic group differences 1063extrathoracic manifestations
1047
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lung adenocarcinoma (cont.)fetal 1073–7, 1076, 1077, 1078gender 1047gene amplifications/deletions
1064genetics 1045–6, 1045genomic imbalances 1045grading system 1056ground-glass nodules 1048–9,
1048histopathology 1051–6, 1066immunohistochemistry 1025,
1028, 1048, 1061, 1065–6incidence 889, 1046intrathoracic spread 1047invasive 1050, 1055, 1059mucinous 1066–8, 1067,1069, 1073
variants 1044–5, 1050–1,1055, 1057, 1058, 1059
karyotypic changes 1045, 1045KRAS gene mutations 924,
924, 1062–3lepidic predominant 918, 1044,
1055location 1047macroscopic pathology 1049–51mesothelioma 1491–2, 1494–5differential diagnosis 1494,1500, 1508–9
metastases 1028, 1047, 1049microinvasive 1054micropapillary predominant
1055minute pulmonary
meningothelial-likenodule association 1228
mixed subtype 1044, 1053molecular markers 1066molecular pathology 1061–4,
1062morphology 1053–4mucin globules 1476mucinous 1029, 1044, 1068,
1070differential diagnosis 1068epidemiology 1066invasive 1066–8, 1067, 1069,1073
KRAS mutations 1063, 1068prognosis 1068radiography 1066–7treatment 1068
mucoepidermoid carcinomadifferential diagnosis 1132
multifocal 1064, 1064natural history 1066nodules 1048–9, 1049non-smokers 1046–7, 1046non-terminal respiratory
unit 1045p63 immunohistochemistry
1061papillary predominant 1054–5parenchymal 910
pediatric 1047PET imaging 1049primary in children treated for
malignancy 1047prognosis 1066pseudomesotheliomatous 1051radiographic findings 1047–9,
1048, 1049screening 1047small cell lung carcinoma
differential diagnosis1167
smoking 1066solid predominant 1055squamous cell carcinoma
differential diagnosis1027, 1029
STK11/LKB1 gene mutation1063
subtypes 1045, 1046, 1053surfactant protein A 1025symptoms 1047tail sign 1047terminal respiratory unit 1045,
1046thyroid transcription factor 1
expression 1016, 1017,1061
treatment 1066typical carcinoid tumor
differential diagnosis1167
variants 1044–5, 1050–1,1066–79
visceral pleural invasion 1064see also adenocarcinoma
in situ (AIS), mucinouscystadenocarcinoma
lung adenosquamous carcinoma1063, 1093
lung agenesis 68, 74–5bilateral 74, 75unilateral 74–5
lung allocation score (LAS), lungtransplantation 767–8
lung cancer 945–79age 948alcohol ingestion 958a-1-antitrypsin deficiency 957apical 970arsenic exposure 952–3asbestos exposure 525–8, 953,
957diagnosis 526–7electron microscopy 526,527–8
risk 526smoking 525, 526tissue analysis 527–8
asbestos fiber burden 526asbestos fiber potency 525–6asbestosis association 525, 526asthma association 957autofluorescence
bronchoscopy 977
beryllium exposure 541bronchoscopy 976–7carcinoma with rhabdoid
phenotype 1171chest X-rays 965, 975–6chronic eosinophilic
pneumonia 572classification 889clinical manifestations 968–75coal workers’ pneumoconiosis
536connective tissue disease 804,
958COPD 957CREST syndrome 823CT scans 967, 968, 969, 976cytochrome P450 enzymes 949cytology 978dermatomyositis 827diagnostic methods 976–8diet association 958–60EGFR 50encephalomyelitis 973–4endocrinologic syndromes 972environmental pollution 951–2epidemiology 889, 945–50Epstein–Barr virus 956etiology 950–60familial 960, 965FDG-PET 976fine-needle aspiration 977flavonoid risk reduction 959folded lung differential
diagnosis 1451frozen sections 978gastrointestinal pseudo-
obstruction 974gender distribution 945, 947–8genetic risk 961genetic susceptibility 960–5genome-wide studies 963–5geographic trends 946hematologic syndromes
972, 975high-resolution computed
tomography 965histology 949–50HIV infection 956human papilloma virus 953–6hypertrophic pulmonary
osteoarthropathy 973hyponatremia of malignancy
972idiopathic pulmonary fibrosis
957–8immunohistochemistry 50immunosuppressed patients
956incidence 119, 889, 945–6infections 953–7inflammation association 957intraoperative palpation and
wedge resection 978intrathoracic spread 969–70invasive 901–2
isolated tumor cells 1012KRAS gene mutations 951Lambert–Eaton syndrome 974large specimen evaluation 47–9lung injury 957–8lymph node involvement 13,
970, 1007mediastinoscopy 977mesothelioma differential
diagnosis 1508–9metastases 970–1, 971, 1007,
1011mortality 945–6, 947MRI 976mucorales 239–41clinical features 240diagnosis 241differential diagnosis 241epidemiology 240organisms 239pathology 240prognosis 241treatment 241
multiple synchronous primarytumors 1012
mycobacterial infections 956–7neoadjuvant therapy 594–5nodules 1012non-smoking related 945–6occupational factors 952–3,
954, 955oxidative stress 958p53 gene mutations 951paraneoplastic syndromes
971–5, 972phytosterols 960pleomorphic and KRAS
mutations 1063pleura histologic sampling
1005pleural effusion examination
977pleural invasion 48, 1005polymyositis 827pre-existing lung lesions 890prognosis 978–9, 1013, 1020nodal disease 1011
race 948–9, 949radiation therapy with
chemotherapy 594–5, 595radiofrequency ablation 595radiography 975–6, 975,
976, 977radon exposure 951relapse 978–9rheumatoid arthritis 814rhinosinusitis 957risk after head and neck
cancer 946risk with pleural plaques 1443scleroderma 822–3screening 965–8, 966, 967, 969secondary pneumothorax
1415–6signs/symptoms 969, 969, 971
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single gene polymorphisms960–3
smoking association 890–1,946, 947–8, 950–1
socioeconomic factors 950solid fuel use 946staging 48–9, 1004, 1007, 1009,
1010, 1011subacute sensory neuropathy
973–4survival 978, 1013talc miners 538TNM classification 1004carcinoid tumor 1012clinical 1004M category 1004, 1011, 1011multiple synchronousprimary tumors 1012
multiple tumor nodules1006, 1012
N category 1004, 1007, 1008original descriptors 1012pathologic 1004resection completeness 1013small cell lung cancer 1012specific situations 1013survival 1013T category 1004, 1005, 1006visceral pleural invasion1005
total burden 945traffic-related pollution 952treatment 978–9tuberculosis 956–7tumor extension 970tumor growth rate
determination 968tumor measurement 1005tumor nodules 1006tumor size 1005uranium miners 891, 953venous thromboembolism 975vermiculite-associated 539–40video-assisted thoracoscopic
surgery 977visceral pleural invasion 971,
1005vitamin A deficiency 958–9volume doubling time (VDT)
968welder’s pneumoconiosis 549see also lung adenocarcinoma
lung malformations 74–95classification 76congenital lobar emphysema
85–6congenital pulmonary
lymphangiectasis 87–8herniation 75pulmonary agenesis 74–5pulmonary cystic disease 75–82pulmonary hyperplasia 86–7pulmonary hypoplasia 91–3pulmonary sequestration
82–4
lung tissueabnormal 90–1ectopic 90–1, 91
lung transplantation 767–95adenovirus 784–5, 784airway anastomotic
complications 772–3airway inflammation without
scarring 780–1allograft rejection 769antibody-mediated rejection
768, 769, 781–3artificial lung technology 795Aspergillus infection 229, 785,
786bronchiolitis obliterans 768,
790–2bronchiolitis obliterans
syndrome 782–3, 790–2bronchoalveolar lavage 770bronchopneumonia 774Candida infection 785chronic vascular rejection
792–3, 794cytomegalovirus infection 777,
783–4, 784drug-induced lung disease 790early post-transplant period
770–4Epstein–Barr virus infection
778, 786–9ex vivo lung perfusion 795fungal infection 785graft failure 768, 772herpes simplex virus 784–5histological assessment 769–70hyperacute rejection 768,
771–2, 773illicit drug abuse 790indications 767, 768infections 770, 773–4,783, 783–9intermediate period after
774–90ischemic–reperfusion injury
770–1Langerhans’ cell histiocytosis
790late period 790–5lung allocation score 767–8lymphangioleiomyomatosis
793–5, 1255lymphocytic bronchiolitis
780, 781open lung biopsy 770pathologists’ role 768, 768–9pediatric population 768peri-operative period 770–4Pneumocystis jirovecii
pneumonia 785post-ischemic scarring 773primary graft dysfunction 770–1procedure types 767procedures performed 767pulmonary allograft
monitoring 769–70
recurrent disease in allograft793–5, 794
respiratory bronchiolitis 790smoking-related lesions
790, 791temporal approach to
pathology 770, 771transbronchial biopsy 769–70vascular anastomotic
complications 772–3viral infections 770, 783–5community-acquired 785
see also acute cellular rejectionin lung transplantation,post-transplantlymphoproliferativedisease (PTLD)
lung tumors 118–26antibodies, specificity 1015electron microscopy 50immunohistochemistry 50, 1015cytokeratins 1027Napsin A 1023, 1026neuroendocrine markers1026, 1027
p16 protein 1027p63 protein 1027, 1060, 1061rapid technique for frozensections 1023
surfactant protein A 1025,1026
surfactant protein B 1025,1026
immunoperoxidase indiagnosis 1015
incidence 119thyroid transcription factor 1
expression 1016staining 1023
lupusacute pneumonitis 815drug-induced 589–90, 819,
1426–7, 1427see also systemic lupus
erythematosus (SLE)lymph nodes 12AJCC/UICC Lung Cancer
Staging system 48–9,1007–11
aspirates 41–2, 1317–23hilar region of bronchi 9metastatic spread in
intrathoracic 1391–4see also intra-pulmonary
lymph nodes (IPLN)lymphangiectasia 76, 1259congenital 86, 87–8
lymphangioleiomyomatosis857–8, 1249–55, 1251
age factors 1250cell of origin 1249classification 1249clinical features 1250clinicopathologic correlation
1254
cysts 1250, 1252cytology 1253differential diagnosis 1254–5diffuse pulmonary
lymphangiomatosisdifferential diagnosis1259
electron microscopy 1253–4estrogen receptor positivity
1253extra-pulmonary 1252genetics 1249–50histopathology 1250–2, 1252HMB-45 immunostain 1253immunohistochemistry 1253insulin-like growth factor
binding proteins 1253light chain deposition disease
differential diagnosis 1340lung transplantation 793–5,
1255macroscopic pathology 1250matrix metalloproteinase
activity 1253micronodular pneumocyte
hyperplasia 1252molecular findings 1254natural history 1255progesterone receptor
positivity 1253prognosis 1255radiographic findings 1250secondary pneumothorax
1415, 1416treatment 1255TSC gene mutations 1249–50,
1254tuberous sclerosis complex
1249–50, 1252two-hit mechanism 1254
lymphangiomas 864, 1259, 1513lymphangiomatosis 1513see also diffuse pulmonary
lymphangiomatosislymphangitic carcinomatosis
1382–4lymphatic drainage of lung 12lymphatic dysplasia syndrome
1259–60lymphatic filariases 308–11clinical features 309diagnosis 310–11epidemiology 308organism 308–9pathogenesis 311pathology 309–10
lymphatic stomata 31, 1408, 1409lymphatics 11, 665see also lymph nodes
lymphocytic bronchiolitis 780,780, 781, 781
lymphocytic (lymphoid)interstitial pneumonia(LIP) 200–1, 367, 463,823, 1316, 1319–21
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lymphocytic (lymphoid)interstitial pneumonia (LIP)(cont.)associated diseases 1319, 1319benign pulmonary lymphoid
proliferations 1318clinical features 1320connective tissue disease
association 463differential diagnosis 1320–1EBV infection 1320HIV infection 264, 1319, 1320hypersensitivity pneumonitis
differential diagnosis 463immunohistochemistry 1320lymphoid hyperplasia 1318marginal zone lymphoma
differential diagnosis1329
nonspecific interstitialpneumonia differentialdiagnosis 1321
pathology 1320, 1320prognosis 1320radiologic features 1320rheumatoid arthritis 811, 811Sjögren syndrome 823–4,
1319, 1320systemic lupus erythematosus
816treatment 1320
lymphocytic interstitialpneumonitis 804
lymphoepithelioma-likecarcinoma (LELC)1119–20
cytology 1119differential diagnosis 1119–20EBV expression 1120epidemiology 1119genetics 1119pathology 1119, 1120prognosis 1120
lymphohistiocytoidmesothelioma 1490
lymphoid hyperplasia 812–13,824, 825, 1322
lymphoid infiltrates 1028lymphoid tissue 1316–7lymphoma 126, 1324–45anaplastic large cell 1343B-cell lymphomas 1324–43,
1346age-related EBV-associated1344
common variableimmunodeficiency 1344
cytotoxic drugs 1345histogenesis 1324HIV/AIDS-related 1344immunocompromised patients
1344large cell carcinoma rhabdoid
phenotype differentialdiagnosis 1121
lymphoepithelioma-likecarcinoma differentialdiagnosis 1119–20
lymphoid hyperplasia 1318metastases 1401pleural 1354, 1514secondary 1357
secondaryclinical features 1345pleural 1357pulmonary changes 1345
T-cell lymphomas 1343, 1344,1346
see also specific namedlymphomas
lymphomatoid granulomatosis(LYG) 1331–6
classification 1334, 1334clinical features 1332EBV infection 199, 1334HIV infection 1332Hodgkin lymphoma
differential diagnosis1342
immunocompromised patients1332
immunohistochemistry 1334,1335
inflammatory infiltrate 1334pathology 1332, 1333, 1334,
1334treatment 1336vascular infiltration 1332Wegener’s granulomatosis
differential diagnosis 729lymphoplasmacytic lymphoma
(LPL) 1331lymphoproliferative disorders
126, 1316–57benign lymphoid
proliferations 1317–23classification 1316histiocytic disorders 1354rheumatoid arthritis 814see also lymphoma
lysinuric protein intolerance427–8
clinical manifestations 427electron microscopy 428epidemiology 427genetics 427laboratory findings 428pathology 427–8pathophysiology 428prognosis 428radiological findings 427, 427treatment 428
lysosomal storage diseases 409–27Fabry disease 417–18Farber disease 426–7Gaucher disease 409–14GM1 gangliosidosis 423Hermansky–Pudlak syndrome
418–21Krabbe disease 423–5
mucopolysaccharidoses 421–3Niemann–Pick diseasetype A and B 414–16type C 416–17
Pompe disease 425–6storage cells 413
Macleod’s syndrome 86macrophage mannose receptor
(MMR) 28macrophagesactivated exudate 185acute lung injury 353, 354ceroid-filled 420, 421chronic eosinophilic
pneumonia 569cigarette smoke-induced 385COPD 611desquamative interstitial
pneumonia 388desquamative interstitial
pneumonia-like reaction388
emphysema 620foamy 414–15, 416–17GM1 gangliosidosis 423hemosiderin-laden in
Goodpasture’s syndrome737
iron-laden 52Krabbe disease 424lysinuric protein intolerance 428marijuana abuse 597mycobacteria ingestion 212, 213respiratory fibrosis/RB-ILD
385, 386–7smokers 27smoking 385see also alveolar macrophages
malakoplakia 178–9, 412, 1242malaria 297–300clinical features 298diagnosis 299–300differential diagnosis 300drug toxicity 300Duffy blood group 297epidemiology 297histology 299life cycle 298organism 297–8pathogenesis 297, 299pathology 298–9, 299treatment 300
Malassezia furfur complex274–7, 276
catheter-associated 276clinical features 276diagnosis 277epidemiology 275–6pathology 276transmission 275–6
malignancyatypical mesothelial
hyperplasia distinction1453–4
connective tissue disease 804dermatomyositis 827idiopathic pulmonary fibrosis
association 372molecular evolution 929pleural exudate 1412polymyositis 827pulmonary artery embolism
684riskcongenital adenomatoidmalformations 79
diffuse pleural fibrosis 1448pleural plaques 1443
sarcoidosis-like granulomas491
sarcoidosis-like reaction 490Sjögren syndrome 825Wegener granulomatosis 715malignant
angioendotheliomatosissee intravascular largeB-cell lymphoma
malignant lymphomasee lymphoma
malignant melanomaclear cell tumor of the lung
differential diagnosis 1258large cell carcinoma rhabdoid
phenotype differentialdiagnosis 1121
lymphoepithelioma-likecarcinoma differentialdiagnosis 1120
mesothelioma differentialdiagnosis 1513
metastatic 1288, 1384, 1388,1391, 1401
diagnosis 1032, 1401differential diagnosis 1401intrathoracic lymph nodes1393
morphologic variability 1401treatment 1401
pleomorphic carcinomadifferential diagnosis 1194
pleural 1513primary pulmonary 1286–8,
1287, 1401primary pulmonary
angiosarcoma differentialdiagnosis 1273
spindle cell carcinomadifferential diagnosis 1194
malignant mesotheliomasee mesothelioma
malignant peripheral nervesheath tumor 1518–9
malignant small cell tumor of thethoracopulmonary region1170
malinosculation 76Mallory’s hyaline-like material
in type II pneumocytes56, 56
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MAML2 gene mutations,mucoepidermoidcarcinoma 1131, 1132
Mammomonogamus laryngeus(mammomonogamiasis)322
man-made fibers 550–1dimensions 550–1epidemiology 551physicochemical
characteristics 551types 550see also refractory ceramic
fibers (RCF)manganese superoxide dismutase
(MnSOD) 1465maple bark stripper’s lung 453,
453Marfan’s syndrome 428–9, 1415clinical features 428electron microscopy 429epidemiology 428genetics 428pathology 429, 429pathophysiology 429prognosis 429radiological findings 428–9,
429treatment 429
marginal zone lymphoma 1318,1326, 1327
cytology 1329immunohistochemistry 1328plasmacytoma differential
diagnosis 1341Sjögren syndrome 825
marginal zone lymphoma,MALT-type 1324–9
amyloid deposition 1326chromosome translocations
1328clinical features 1324–5diagnosis 1325differential diagnosis 1328–9follicular pattern 1325immunohistochemistry 1326–7molecular pathology 1328pathology 1325–6plasma cell differentiation 1326radiographic findings 1325transformation 1326treatment 1329
marijuana abuse 597–8paraquat toxicity 598pathology 597, 597–8
Masson bodies 150, 809Masson–Fontana method 1164mast cell(s) 27, 28, 1283mast cell disease, systemic 1348matrixmetalloproteinases (MMPs)atypical adenomatous
hyperplasia 926localized non-mucinous
bronchioloalveolarcarcinoma 926
mesothelioma 1467preinvasive lesions 906–7
measles 192–3, 193pathology 193pneumonia 183, 193vaccination 193
mechanical ventilation 113air leaks 109, 111ball-valve effect 113
meconium aspiration syndrome112–13
clinical presentation 112definition 112fetal distress 113histopathology 112persistent pulmonary
hypertension of thenewborn association 113
ventilation/perfusionmismatch 112–13
meconium plug 112MECT1 gene mutations,
mucoepidermoidcarcinoma 1131, 1132
medial hyperplasiacongestive vasculopathy 690hypoxic arteriopathy 689plexogenic arteriopathy 674pulmonary capillary
hemangiomatosis 693pulmonary veno-occlusive
disease 693mediastinal lymph nodes,
metastatic pulmonarynodular disease 1393
mediastinal lymphadenopathy1393
mediastinal teratoma 1286pulmonary teratoma
differential diagnosis1286
mediastinal thymoma 1285mediastinum, mesothelioma
invasion 1469megakaryocytes 28, 28, 56–8melanoma see malignant
melanomamelioidosis 178Mendelian cancer syndromes,
lung cancer 960Mendelson’s syndrome 632meningiomametastases 1394see also primary pulmonary
meningiomamercury pneumonitis 550Merkel cell carcinoma of skin
1022, 1400mesenchymal neoplasms 1224–88angiomyolipoma 1255–6benign metastasizing
leiomyoma 1244–7diffuse pulmonary
lymphangiomatosis 1255,1258–61
granular cell tumors 1239–42minute pulmonary
meningothelial-likenodules 1227–30
neurogenic tumors 1239primary pulmonary
chondrosarcoma 1238–9primary pulmonary glomus
tumors 1247–9primary pulmonary leiomyoma/
leiomyosarcoma 1242–3primary pulmonary lipoma
1231–3primary pulmonary
liposarcoma 1233–4primary pulmonary
meningioma 1229,1230–1
primary pulmonary osteogenicsarcoma 1235–6
pulmonary angiomyolipoma1256
pulmonary chondroma 1237–8pulmonary hamartoma 1143–4,
1224–7pulmonary rhabdomyosarcoma
123–4, 1242pulmonary vein sarcoma1243–4see also clear cell tumor of the
lung (CCTL), lymphangioleiomyomatosis
mesenchymal stromal cells,lung-resident (LR-MSC) 4
mesenchymoma see pulmonaryhamartoma
mesothelial cellschemokine production 1412inclusions 1393inflammatory cell recruitment
1410malignant 1474pattern recognition receptors
1410pleural fluid 1408, 1409–10reactive 1474, 1475secretions 1409
mesothelial hyperplasia 32, 1419,1522, 1523
reactive 1453, 1453–4see also atypical mesothelial
hyperplasia (AMH)mesothelioma, atrioventricular
node 1473mesothelioma, malignant pleural
1454–522anatomic sites 1454apoptotic control 1465–6asbestos cell signaling 1464–5asbestos exposure 526, 1438,
1457–61asbestos fiber type 1456–7basal hemothorax 1477benign pleural disease
differentiation 1503–5,1504
biphasic 1480, 1486–7, 1487,1493, 1500–3, 1515–6
buildings with asbestos fibers1458
C-MET 1529calretinin sensitivity 1496–7carcinoma markers 1495–6CD10-positive 1509–10cdk inhibitors 1468chest pain 1468–9chest wall invasion 1476children 1460chromosomal changes 1467–8classification 1469, 1469–71clear cell 1488, 1488–9clinical features 1468–9cyclins 1468cytokeratin-negative 1496cytokeratins 1496, 1498cytology 1473–5, 1474D2-40 1498–9, 1509deciduoid 1487desmin 1505desmoplastic 1447, 1480, 1485,
1486diagnosis 50differential diagnosis 1502,
1508–22distant spread 1478–9E-cadherin 1499EGFR expression 1466electron microscopy 50, 1492–3environmental 1459–60epidemiology 1454–6epithelial membrane antigen
1499, 1504–5epithelioid 1479, 1480–2, 1492diagnosis 1493differential diagnosis 1508–15electron microscopy 1492–3histological subtypes 1481,1482, 1487–90
immunohistochemistry 1482immunohistochemistry inadenocarcinomadistinction 1494–5
well-differentiated papillarydifferential diagnosis1507–8
estrogen receptor b expression1529
familial 1460folded lung differential
diagnosis 1451giant cell 1489–90GLUT1 1500growth factors 1466–7HBME-1 positivity 1499hepatocyte growth factor 1467histochemical stains 1493–4histology 1480–92human milk fat globulins 1499immunohistochemistry 1475,
1494–5, 1504–5incidence 1438, 1455, 1456
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mesothelioma, malignant pleural(cont.)intra-pulmonary spread 1478ionizing radiation 1461–2keratinocyte growth factor 1467Ki-67 proliferation index 1505lactate dehydrogenase 1529latent period from exposure to
asbestos 1464lepidic pattern 1490lipid-rich diffuse 1488localized 1477–8lung adenocarcinoma
differential diagnosis1065, 1494, 1500
lymphohistiocytoid 1491macroscopic pathology 1476,
1476–7markers 1501matrix metalloproteinases 1467mediastinal invasion 1469mesothelioma markers
1496–500metastases 1478–9microcystic 1487–8mortality ratio 1460mucin-positive 1488mucin staining 1493–4multicystic 1476myxoid 1477, 1483N-cadherin 1499nodules 1476non-asbestos causes 1461–3occupational exposure 1457–8oncogenesis mechanisms of
asbestos 1464P13-K/AKT pathway 1466p16/CDKN2A deletion 1529p53 tumor suppressor gene 1504paraoccupational 1458pathophysiology 1528PDGF 1466–7pericardial invasion 1476, 1477pleomorphic 1489, 1489–90pleural plaques 1442–3, 1476podoplanin 1499primary pulmonary osteogenic
sarcoma differentialdiagnosis 1236
prognosis 1528–30radiological findings 1469, 1470reactive oxygen species 1464–5refractory ceramic fibers 1462risk with pleural plaques 1443sarcomatoid 1479, 1482–5differential diagnosis 1485electron microscopy 1493histopathology 1484
sarcomatoid tumor differentialdiagnosis 1516–8
simian virus 40 1462–3small cell 1490solitary fibrous tumor of the
pleura differentialdiagnosis 1435
spread 1478–9squamoid change 1482staging 1469–71Stanton hypothesis 1467synchronous bilateral 1478TGF-b activity 1467thyroid transcription factor 1
negativity 1020tumor suppressor genes 1466,
1467vermiculite-associated 539–40well-differentiated papillary
1505–8clinical features 1505–6cytology 1507differential diagnosis 1507–8electron microscopy 1507pathology 1506, 1506–7prognosis 1508treatment 1508
Wilms’ tumor gene product1497–8
women 1458zeolite-associated 539see also sarcomatoid
mesotheliomamesothelioma, ovarian 1471–2mesothelioma, pericardial 1471mesothelioma, peritoneal 1458,
1471asbestos exposure 1461benign cystic 1522–3clinical presentation 1471deciduoid 1487desmoplastic 1485differential diagnosis 1485,
1527, 1528in women 1522–8
epithelioid 1479, 1480–2,1487–90
histology 1480–92immunohistochemistry 1527macroscopic pathology 1479–80microcystic 1487–8ovarian serous tumor
differential diagnosis1527, 1528
radiology 1471risk factors 1460–1sarcomatoid 1479, 1482–5Thorotrast exposure 1461well-differentiated papillary
1524mesothelioma, primary hepatic
1473mesothelioma, testicular 1473mesothelioma, tunica vaginalis
1472, 1472–3clinical presentation 1472treatment 1472well-differentiated papillary
1472mesothelioma cells 1467–8, 1474mesothelioma markers 1496–500mesothelium 13, 30–1
microvilli 31physiology 1409pneumothorax 1417structure 31surface proliferation 1415, 1417
metal-associated diseases 513,540–4
metal fume-induced disease546–50
metal-working fluids,hypersensitivitypneumonitis 459, 467
metaplastic bone 54metapneumovirus 117–18, 182metastases 118, 1375–401acinic cell carcinoma
differential diagnosis 1140adenoid cystic carcinoma
1135, 1394, 1382adrenal cortical carcinoma
1382alveolar soft-part sarcoma
1379ameloblastic fibrosarcoma
1394angiosarcoma 1383, 1392benign metastasizing
leiomyoma 1398breast carcinoma 1378, 1382,
1383, 1389, 1395calcification 393, 1378carcinosarcoma 1203cervical cancer 1398cervical lymph nodes 1394chondrosarcoma 1237, 1238–9,
1380chordoma 1387choriocarcinoma 1384, 1399clear cell carcinoma differential
diagnosis 1121clinical features 1376–7colorectal adenocarcinoma
1385, 1396, 1396colorectal carcinoma 1031,
1032, 1396CT imaging 1377dermatofibrosarcoma
protruberans 1392, 1400–1development 1375dormant micrometastases 1375endobronchial 1384–9endometrial carcinoma 1386,
1398endometrial sarcoma 1387stromal 1381, 1398
epithelialhemangioendotheliomadifferential diagnosis1266–7
gastrointestinal stromal tumor1396–7, 1396
gestational trophoblasticdisease 1398–9
giant cell sarcoma differentialdiagnosis 1197
glioblastoma multiforme 1387granulosa cell tumors of ovary
1398growth patterns 1377head and neck cancer 1393,
1394hemorrhage 1378hepatocellular carcinoma
1395–6hydatiform mole 1399immunohistochemistry 50incidence 1376interstitial spread 1391intra-alveolar spread 1391intra-pulmonary lymph nodes
1316intrathoracic nodal spread
1391–4leiomyosarcoma 1382lepidic spread 1390–1, 1396leukemia 1401liposarcoma 1384liver tumors 1395–6lung adenocarcinoma 1028,
1047, 1049lung cancer 970–1, 971, 1007,
1011lung site 1375–6lymphoepithelioma-like
carcinoma differentialdiagnosis 1120
lymphoma 1401malignant melanoma 1288,
1384, 1388, 1391, 1401diagnosis 1401differential diagnosis 1401intrathoracic lymph nodes1393
morphologic variability 1401treatment 1401
mechanical factors 1376meningioma 1394mesothelioma 1478–9differential diagnosis 1509–10
myofibroblastic tumor 1400–1nasopharyngeal carcinoma
1394neuroendocrine carcinoma
1399–400nodular 1377–81non-seminomatous germ cell
tumors 1399non-small cell lung cancer 971osseous osteogenic sarcoma
1235–6osteosarcoma 1389, 1400ovarian cancer 1391, 1397–8pancreatic adenocarcinoma
1385, 1391, 1396pancreatic carcinoma 1396parenchymal nodules 1377–81patterns 1377phyllodes tumor 1395, 1395placental site trophoblastic
tumor 1399
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pleomorphic adenoma 1394pleomorphic carcinoma
differential diagnosis1194
pleuropulmonary blastoma122
prostate adenocarcinoma1399, 1400
pulmonary blastoma 1209pulmonary lymphangitic
carcinomatosis 1382–4radiography 1377renal cell carcinoma 1380,
1397, 1397rhabdomyosarcoma 123route of spread 1376salivary gland carcinoma 1394sarcoma 1400–1sclerosing hemangioma
869, 872seed and soil theory 1376sex cord stromal tumors 1398small cell lung carcinoma 1153soft tissue sarcoma 1400sources 1376spindle cell carcinoma
differential diagnosis 1194spindle cell sarcoma 864squamous cell carcinoma
1094, 1105synovial sarcoma 1283testicular non-seminomatous
germcell tumor 1381, 1399testicular seminoma 1399thyroid carcinoma 1395papillary 861, 872, 1378,1392
tongue carcinoma 1388tumor emboli 1389–90typical carcinoid tumor
differential diagnosis 1167unusual patterns of spread
1390–4urothelial carcinoma 1383,
1393uterine tumors 878–9uterine carcinoma 1384, 1398uterine leiomyoma 1398uterine leiomyosarcoma1398
methotrexate toxicity 590–1, 591drug-induced lymphoma 814,
1345methylphenidate abuse 600mica pneumoconiosis 538, 539Michaelis–Gutman bodies 412micro-aspiration, occult 466micro-CT scanning 48Micrococcus pneumonia 171, 178micronodular pneumocyte
hyperplasia (MNPH) 917see also multifocal
micronodularpneumocyte hyperplasia(MMPH)
microRNAs 908, 1104, 1105, 1466microscopic polyangiitis 729–31ANCA types 731autoantibodies 711clinical manifestations 730cytology 731differential diagnosis 731epidemiology 730genetics 730histopathology 730–1laboratory findings 731macroscopic pathology 730,
730, 731natural history 731pathogenesis 731polyarteritis nodosa differential
diagnosis 744–5prognosis 731radiographic findings 730
microsporidiosissee Encephalitozooncuniculi (microsporidiosis)
Microsporum canis, lung cancerrisk 957
microthrombi 58microvascular endothelial cells 30middle lobe syndrome 632–4, 634miliary nodular lesions 304see also Mycobacterium
tuberculosis (tuberculosis),miliary disease
Miller’s secondary lobules 11mineral dust inhalation 513,
531–2, 646, 647mineral fibers, non-asbestos
550, 550–3mineral pulmonary elastosis 58minimally invasive
adenocarcinoma (MIA)1044, 1053, 1058–9, 1066
mucinous 1068minute pulmonary
meningothelial-likenodules (MPMN) 1227–30
cell of origin 1228classification 1228clinical features 1227–8clinicopathologic correlation
1228differential diagnosis 1229electron microscopy 1228histopathology 1228immunohistochemistry 1228incidence 1227–8macroscopic pathology 1228molecular findings 1228natural history 1230nodules 1228prognosis 1230radiographic findings 1228reticulonodular infiltrates 1228
mitogen-activated protein kinase(MAPK) 1465
mitosis, pulmonary preinvasivedisease 903
mixed connective tissue disease827–8
alveolar hemorrhage 828autoantibodies 827clinical features 827diffuse alveolar damage 828interstitial lung disease 827pathology 827, 828pleural effusion 827–8pleurisy 827–8prognosis 828pulmonary hypertension 827
mixed dust fibrotic (MDF)lesions 532
mixed dust pneumoconiosis(MDP)/mixedpneumoconiosis 532, 532
MOC-31 1495molecular markers 43, 50–1Monge’s disease 686–8monoclonal antibodies (mAb)
592–3, 1021Monod sign, aspergilloma 232mononuclear cells, acute cellular
rejection morphologicalmimic 777
Moraxella catarrhalis 147, 178,171, 172
mordenite 538–9Morquio syndrome 422Mounier–Kuhn syndrome
71, 430mountain sickness, chronic
686–8mTOR signaling 864, 1258mucin(s) 18, 575, 612mucinous cystadenocarcinoma
1044–5, 1070, 1072, 1073mucinous cystadenoma 1072–3mucinous cystic neoplasms
1070–2, 1072mucociliary clearance, aging
effects 32mucociliary escalator, barrier to
bacterial infections 153mucoepidermoid carcinoma
1073, 1127–33adenoid cystic carcinoma
differential diagnosis 1133classification 1127clinical features 1127clinicopathological correlation
1131cytology 1129–30, 1131differential diagnosis 1132–3electron microscopy 1130genetics 1131high-grade 1129, 1131histopathology 1128–9, 1129,
1130immunohistochemistry 1130,
1132low-grade 1128–9, 1129, 1130macroscopic pathology 1127–8,
1128, 1129
mesothelioma differentialdiagnosis 1510
molecular findings 1131natural history/prognosis
1133radiographic findings 1127,
1128sclerosing hemangioma
differential diagnosis 872squamous cell carcinoma
differential diagnosis1104
treatment 1133mucopolysaccharidoses 421–3clinical manifestations 421–2electron microscopy 422, 422epidemiology 421genetics 421laboratory findings 423outcome 423pathology 422pathophysiology 423prognosis 423radiological findings 422treatments 423
Mucorales infections(mucormycosis) 239, 239
abscess 240clinical features 240culture 241diagnosis 241differential diagnosis 241endobronchial 240epidemiology 240organisms 239pathology 240prognosis 241pulmonary artery erosion 241treatment 241
mucosa-associated lymphoidtissue (MALT), marginalzone lymphoma1324–9
mucostasis, impaired carcinogenclearance 957
mucus cells see goblet cellsmucus gland adenoma (MGA)
1073, 1146–8, 1146clinical features 1146–7clinicopathologic correlation
1147definition 1146differential diagnosis 1147histopathology 1147immunohistochemistry 1147macroscopic pathology 1147mucoepidermoid carcinoma
differential diagnosis1132–3
natural history 1148prognosis 1148radiographic findings 1147
mucus retention cysts, tracheal 71Müllerian epithelial neoplasms
1473, 1524–5, 1528
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multifocal micronodularpneumocyte hyperplasia(MMPH) 857–9, 858, 859
cell of origin 857classification 857clinical features 857–8clinicopathologic correlation 859definition 857differential diagnosis 859electron microscopy 859genetics 857, 859histopathology 858immunohistochemistry 858lymphangioleiomyomatosis
857–8macroscopic pathology 858molecular findings 859natural history 859prognosis 859radiographic findings 858
multiloculated peritonealinclusion cysts (MPIC)1522–3
multiple endocrine neoplasia(MEN), Carney’s triad1237
multiple myeloma 1340muscle dysfunction, COPD 623MUTYH-associated polyposis
960myasthenic syndrome 1153mycobacterial infections 206–23antigen presentation 213antigen processing modulation
212–13atypical (environmental) 206,
220, 222, 412, 458clinical signs 209diagnosis 207–8epidemiology 206–7management 223pathogenesis 213–14pathology 218–20radiological features 211
clinical management 222–3culture 207delayed-type hypersensitivity
reactions 213, 217differential diagnosis 221–2DNA sequences 208–9granular cell tumor differential
diagnosis 1242granulomas 213host genes 213host response 212lung cancer 956–7macrophage ingestion 212, 213microbiological diagnosis
207–9natural history 223pathogenesis 212–14pathology 214–22phagosomes 212–13prognosis 223serological tests 208
T cells 213TNFa 213virulence factors 212
Mycobacterium avium–intracellulare complex211, 218, 219–20,412, 458, 633–4
Mycobacterium immunogenum459
Mycobacterium kansasii 208Mycobacterium tuberculosis
(tuberculosis) 206advanced changes 214antibiotic resistance 208–9aspiration of necrotic
material 217bronchopneumonia 217, 217calcified hilar lymph node 216caseous necrosis 216cavitated pulmonary 217childhood epituberculosis 218clinical features 209clinical management 222–3clinicopathologic correlation
219–20delayed-type hypersensitivity
reactions 217diagnosis 207–9, 222diagnostic tests 208differential diagnosis 221–2diffuse pleural fibrosis 1447directly observed therapy
222–3drug-resistant 223drug side effects 223endobronchial 217, 219epidemiology 206gene sequence 209genome 209granulomatous inflammation
in lymph nodes drainingcancer 222
granulomatous pleural disease1423–4
hilar lymphadenopathy 212histopathology 214HIV coinfection 206, 209,
211, 223incidence 207inflammatory cell interactions
213laboratory investigations 209–10latent 209, 223lung cancer risk 956–7lymphadenopathy 212macroscopic pathology 214management 206mediastinal lymph node
disease 222miliary disease 209, 211, 211,
217, 218multi-drug resistant 206,
208–9, 223natural history 223necrotizing granuloma 215
nodal disease 211non-necrotizing granuloma 215pathogenesis 212–14pathological features 214–18pathology 214–22pleural disease 1423–4pleural effusion 210–11, 211,
217–18, 222, 1412pleural exudate 1412prevention 223primary pulmonary 216prognosis 223pulmonary syndromes 209radiological manifestations
210–11, 210, 211reactivated lesion 217secondary pneumothorax
1415–6secondary pulmonary
216–18, 219silicosis 529spindle cell pseudotumor
218, 219Takayasu arteritis association
748vasculitic process 215
Mycobacterium tuberculosiscomplex 206
Mycoplasma pneumoniaepneumonia 147, 176
mycosis fungoides 1346, 1346granulomatous variant 1346
mycotic infections see fungalinfections
myelodysplastic syndrome 1348myelofibrosis, chronic 1348myeloid leukemia 1347, 1347myeloid metaplasia 1348myeloid sarcoma 1347myeloperoxidase antibodies 711Myers–Kouwenaar body 310myoepithelial cells, epithelial–
myoepithelial carcinoma1136–7
myofibroblastic tumor 124–5,125, 126, 1278, 1400–1
myofibromatosis 125myxoid chondrosarcoma 1521myxoma 1273–4, 1522
N-acetylcholine receptor,nicotine addiction 964
N-cadherin 1499, 1503Napsin A 1023, 1066, 1103, 1190cytoplasmic staining 1023expression 1023, 1026
nasopharyngeal carcinoma,metastases 1386, 1394
NAT2 gene mutations, pleuralplaques 1440
Necator americanus 316necrotic nodule, solitary 314necrotizing sarcoid
granulomatosis 494,495, 1424
bronchiolitis obliterans 496diagnostic criteria 495differential diagnosis 498epidemiology 495laboratory findings 496natural history 498pathogenesis 497pathology 495, 496, 497prognosis 498radiographic findings 495vasculitis 495, 497, 498
Neisseria, pneumonia 178Neisseria meningitidis 172Neisseria mucosa 172botryomycosis 172
nematodes 221, 308–22neonatespulmonary vascular anatomy
666see also infants, perinatal lung
pathology, persistentpulmonary hypertensionof the newborn
nephrotic syndrome, pleuraleffusion 1411
nerve supply to lungs 12neural cell adhesion molecule
(NCAM) 1026, 1027,1164
neural neoplasms 1519neuroblastoma, metastatic 1519neuroendocrine antigens
1164–5neuroendocrine carcinoma,
metastases 1399–400neuroendocrine carcinoma of
lung, grades 1152neuroendocrine cell(s) 19–22, 20,
114–15bronchial 20bronchopneumonia 20, 21fetal lung 20neurosecretory vesicle 21–2, 22nodular aggregates 1172–3peritumoral proliferation
1177–8proliferative lesions 21, 22,
1152, 1172–8reactive proliferation 1172–3tumorlets 1172–3
neuroendocrine cell hyperplasiaof infancy 114–15, 641,1172
neuroendocrine hyperplasia,constrictive bronchiolitis641
neuroendocrine markers 1026,1027
neuroendocrine tumors 1151–78classification 1151–2clinical features 1152–3, 1154cytology 1157–64desmoplastic small round cell
tumor 1171diagnostic criteria 1152
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differential diagnosis 1167–9electron microscopy 1166–7extrapulmonary metastatic
1168genetics 1166–7histopathology 1157–64immunohistochemistry 1164–5lung carcinoma with rhabdoid
phenotype 1171macroscopic pathology 1155natural history 1169paraganglioma 1167, 1171–2precursor lesions 1151primitive neuroectodermal
tumor 1170–1prognosis 1169radiographic findings 1153–7spectrum 1151, 1152see also carcinoid tumor, diffuse
idiopathic pulmonaryneuroendocrine cellhyperplasia (DIPNECH),large cell neuroendocrinecarcinoma (LCNEC),non-small cell carcinomas,with neuroendocrinedifferentiation,pleuropulmonaryblastoma, small cellcarcinoma, small cell lungcarcinoma (SCLC)
neuroepithelial bodies (NEBs)19, 20, 20, 910
neurogenic tumors 1239neuron-specific enolase (NSE)
21, 1027, 1164–5neurosecretory vesicle, pulmonary
neuroendocrine cells21–2, 22
neutropenia, Aspergillus infection229
neutrophil(s)acute lung injury/ARDS 346,
351–3, 354ANCA interactions 711, 729asthma 566Behçet syndrome 751COPD 611emphysema 620function 153usual interstitial pneumonia/
idiopathic pulmonaryfibrosis 373
viral infections 185Wegener granulomatosis 728
neutrophilic capillaritis 450nicotineactivation 964addiction 964clearance 950–1
Niemann–Pick cells 413, 414–15,416–17
Niemann–Pick disease, typeA and B 414–16, 414
clinical manifestations 414
cytology 415differential diagnosis 416electron microscopy 415, 415epidemiology 414genetics 414laboratory findings 415natural history 416pathology 414–15, 415pathophysiology 416prognosis 416radiological findings 414
Niemann–Pick disease, type C416–17
clinical manifestations 416epidemiology 416genetics 416laboratory findings 417pathology 416–17pathophysiology 417prognosis 417radiological findings 416treatment 417
nitric oxide (NO) 113, 1409nitric oxide synthase, inducible
(iNOS) 1409nitrofurantoin toxicity 592nitrogen oxide, lung
adenocarcinomaassociation 952
nitrosamines 891NK/T-cell lymphoma, nasal type
1335NKX2–1 amplification 1064Nocardia asteroides 166, 167, 177abscess 166granulomatous reaction 167in multinucleated giant cell 167
nodular density, wedge biopsy 44nodular lymphoid hyperplasia
825, 1321–2, 1322benign pulmonary lymphoid
proliferations 1318clinical features 1321differential diagnosis 1321–2pathology 1321
non-Hodgkin lymphoma 825non-small cell carcinomaswith giant cells 1197with neuroendocrine
differentiation 1170non-small cell lung cancer
949, 978, 1285age 948metastatic sites 971
nonspecific interstitialpneumonia (NSIP) 114,201, 367, 374–9, 445,463, 524
alveolar cell hyperplasia 916asbestosis differential
diagnosis 522associated conditions 376cellular 376–7, 378, 588classification 376clinical presentation 375
connective tissue diseasepattern of involvement804
dermatomyositis 826desquamative interstitial
pneumonia differentialdiagnosis 389
differential diagnosis 377–8drug-induced lung disease
587–8fibrotic 377, 378genetics 368histological features 377histological pattern 375HIV infection 266hypersensivity pneumonitis
451, 455lymphoid interstitial
pneumonia differentialdiagnosis 1321
lymphoid proliferation 1318mixed cellular/fibrotic 376natural history 379pathogenesis 379pathology 375–7, 376polymyositis 826, 826prognosis 379radiological findings 375,
375, 444respiratory bronchiolitis/
RB-ILD differentialdiagnosis 387
rheumatoid arthritis 809, 810scleroderma 821–2, 821Sjögren syndrome 823, 824systemic lupus erythematosus
818undifferentiated connective
tissue disease 829Noonan syndrome,
congenital pulmonarylymphangiectasis 87
NPC gene mutations 416nuclear factor-kB (NFkB) 153,
906, 1465, 1466nucleic acid amplification tests
(NAATS) 208nucleophosmin 904nuisance dusts 545–6nylon flock worker’s lung 551, 553
obesity, lung cancer risk 960obliterative bronchiolitis 186,
640–3, 792, 793bronchiectasis 794clinical features 811constrictive 553, 641–3differential diagnosis 792etiology 812histologic features 792, 794, 811lung-resident mesenchymal
stromal cells 4lung transplantation 768, 790–2necrotizing sarcoid
granulomatosis 496
occupational 553patterns 793prognosis 812proliferative 640rheumatoid arthritis 811–12,
812treatment 792Wegener granulomatosis 726–7
obstructive sleep apnea, Marfansyndrome 428
occult micro-aspiration 466occupational lung disease 512–53aluminum lung disease 549asbestos 512–28barium pneumoconiosis 546benign pneumoconiosis 545–6beryllium exposure 540–1cadmium pneumonitis 550carbon fibers 551–3coal/coalmine dust 532–6dental technician’s
pneumoconiosis 545economic cost 512food flavorer’s lung disease
553hard metal lung disease 541–3lung cancer occupational
factors 952–3, 954, 955man-made fibers 550–1mercury pneumonitis 550metal-associated diseases
513, 540–4metal fume-induced disease
546–50mineral dust inhalation 513,
531–2mixed dust pneumoconiosis/
mixed pneumoconiosis532, 532
non-asbestos mineral fibers550–3
non-asbestos silicatoses 536–40nuisance dusts 545–6nylon flock worker’s lung 551pathologic response to agents
512popcorn worker’s lung disease
553rare earth pneumoconiosis
544–5silicon carbide
pneumoconiosis 544silicotic lung disease 528–32stannosis 546titanium pneumoconiosis
545–6welder’s pneumoconiosis
547–9Odland bodies, squamous cell
carcinoma 1103oligohydramnios, pulmonary
hypoplasia 91–2, 93Onchocerca volvulus
(onchocerciasis) 308, 322oncocytic metaplasia 54
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oncocytoma 1147, 1148, 1148oncogenes 907open lung biopsy, lung
transplantation 770organ transplantationamebiasis 294CMV antigen 196CMV risk 195immunosuppressive drugs 1348Kaposi’s sarcoma 1268lung cancer risk with
immunosuppression 956microsporidiosis 304see also lung transplantation,
post-transplantlymphoproliferativedisease (PTLD)
organic toxic dust syndrome439, 443, 491
organization of lungs 7–13blood supply 10–11, 28–30fissures 8lobes 8lymphatics/lymph nodes 11–12nerve supply 12pleura 12–13, 30–1size 8structural anomalies 8weight 8
organizing pneumonia (OP)connective tissue disease pattern
of involvement 804dermatomyositis 826, 826drug-induced lung disease 588hypersensitivity pneumonia
differential diagnosis 463inflammatory bowel disease
833–4lung-resident mesenchymal
stromal cells 4nonspecific interstitial
pneumonia pattern 378pathology 588polymyositis 826progression to interstitial
fibrosis 371rheumatoid arthritis 809, 810Sjögren syndrome 824steroid therapy 809systemic lupus erythematosus
819see also acute fibrinous
organizing pneumonia(AFOP), cryptogenicorganizing pneumonia(COP)
Orientia tsutsugamushipneumonia 179
ornithosis 148, 175oropharynx, bacterial
colonization 153osseous osteogenic sarcoma
metastases 1235–6ossifying periostosis 973osteogenic sarcoma 1521
osteopontin 368, 1529–30osteoporosis, COPD 622osteosarcomametastatic 1389, 1400pulmonary 1236see also primary pulmonary
osteogenic sarcomaovarian cancer, metastases 1391,
1397–8ovarian serous tumors 1527, 1528overinflation, biopsy artefact 51oxidative stresslung cancer 958preterm infants 108–9
p-glycoprotein(s) 1235p14arf 904p16/CDKN2A deletion in
mesothelioma 1529p16 gene function loss 905,
907, 909p16 protein 904–5, 923, 1027p21 protein 922p27 protein 925p53 proteinatypical adenomatous
hyperplasia 922–3function 903pulmonary preinvasive disease
903–4squamous dysplasia/
carcinoma-in-situ 904p53 tumor suppressor geneatypical adenomatous
hyperplasia 923BaP diol epoxide 951carcinosarcoma 1204gene mutations 903–4large cell carcinoma 1115lung cancer 951mesothelial hyperplasia
1453–4mesothelioma 1504pleomorphic carcinoma 1190pulmonary blastoma 1213squamous cell carcinoma
1103p63 protein 904atypical adenomatous
hyperplasia 923immunohistochemistry 1027lung adenocarcinoma 1061pleomorphic carcinoma 1190squamous cell carcinoma
immunohistochemistry1103
p170 glycoprotein 1505pachypleuritis see diffuse pleural
fibrosisPagetoid reticulosis 1346pAKT 905Pancoast tumor 970, 970, 976,
1094–5pancreatic adenocarcinoma,
metastases 1385,1391, 1396
pancreatitis, autoimmune 1420panniculitis, COPD 622Panton–Valentine Leucocidin
(PVL) toxin 148papillary adenoma 859–62, 860atypical adenomatous
hyperplasia differentialdiagnosis 917
cell of origin 859classification 859clinical features 859clinicopathologic correlation
861cytology 860–1, 860, 861definition 859differential diagnosis 861electron microscopy 861etiology 859histopathology 860immunohistochemistry 861lung adenocarcinoma
differential diagnosis1065
macroscopic pathology 860molecular findings 861natural history 861–2prognosis 861–2radiographic findings 860sclerosing hemangioma
differential diagnosis 872papillary carcinoid tumor 861papillary cystadenoma 861papillary predominant
adenocarcinoma 1054–5papillary thyroid carcinoma 1377metastatic 861, 872, 1378, 1392
Paracoccidioides brasiliensis(South Americanblastomycosis) 262–4, 262
acute disease 263antigen detection tests 264blastomycosis differential
diagnosis 257clinical features 263culture 263diagnosis 263–4differential diagnosis 264dissemination 263enzyme immunoassay 264epidemiology 262–3immunodiffusion test 263–4inflammatory response 263mucocutaneous lymphangitis
263organism 262pathology 263progressive pulmonary
disease 263serological tests 263–4subacute disease 263treatment 264
paraganglioma 1167, 1171,1171–2, 1249
Paragonimus (paragonimiasis)326–8
clinical features 326–7diagnosis 327–8eggs 327epidemiology 326organism 326, 326, 327pathology 327, 327radiological features 326–7
parainfluenza viruses 184, 192,192
bronchiolitis 192diagnosis 192pathology 192
paraneoplastic cerebellardegeneration 974
paraneoplastic pemphigus 1278paraneoplastic syndromescentral nervous system 973–4cutaneous 974dermatomyositis 827, 974–5hypoglycemia 1431large cell carcinoma 1114lung carcinoma 971–5polymyositis 827retinopathy 974small cell lung carcinoma 1153solitary fibrous tumor of the
pleura 1431squamous cell carcinoma 1094
paraquat toxicity 598, 598parasitic disease 288–335, 736, 1425see also named organisms and
taxonomic groupsparathyroid hormone (PTH) 971parathyroid hormone-related
peptide (PTHrP) 971parenchymal nodules, metastases
1377–81particle mass (PM) 952Pasteurella multocida
pneumonia 173, 178pathogen-associated molecular
patterns (PAMPs)229–30
pattern recognition receptors153, 229–30, 1410
PE-10 1026, 1026pemetrexed, contraindication in
squamous cell carcinoma1104
Penicillium marneffei(penicilliosis marneffei)228, 249
pentastomiasis 334, 335Peptostreptococcus 159, 175pergolide mesylate 1445peribronchial interstitial
fibrosis 391peribronchiolar metaplasia 391,
646–8, 648, 917, 918atypical adenomatous
hyperplasia differentialdiagnosis 917
hypersensitivity pneumonitisdifferential diagnosis 464
pathophysiology 646–8
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prognosis 648treatment 648
pericytes 30perinatal lung pathology 102–13air leaks 109–11embolism 112hyaline membrane disease
103–6meconium aspirate syndrome
112–13persistent pulmonary
hypertension of thenewborn 113
pleuropulmonary blastoma119–23
pneumothorax 109–11pulmonary hemorrhage 111–12pulmonary interstitial
emphysema 109–11respiratory distress syndrome
103–6surfactant metabolic
dysfunction 106thrombosis 112ventilation 109, 111Wilson-Mikity syndrome 109see also bronchopulmonary
dysplasiaperipheral lung
adenocarcinogenesis921–2, 927–8, 929
peripheral lung cyst 81peripheral lung epithelium,
carcinogenesis 909–10peripheral nerve sheath tumors
1518–9peritoneal angiomatoid tumor
1524peritoneal carcinoma, primary
1527peritoneal dialysis, pleural
effusion 1411peritoneal inclusion cysts
1522–3, 1524peritoneal serous carcinomahigh-grade 1526–7low-grade 1526
peritoneal serous lesions 1524–5peritoneal serous tumors 1526,
1527perivascular epithelioid cell
neoplasms (PEComas)1256–8
persistent pulmonaryhypertension of thenewborn 113
nitric oxide 113nitric oxide therapy 113vascular resistance 113
Peutz–Jeghers syndrome,STK11/LKB1 gene 1063
Pfeiffer syndrome, trachealstenosis 68
PGP9.5 1026phaeohyphomycoses 277–8, 277
diagnosis 278etiology 277–8organisms 277subcutaneous 277treatment 278
phagosomes, mycobacterialinfections 212–13
phenethylamine-derived drugabuse 600
phosphatidylcholine 25–6phosphatidylcholine 3-kinase
(P13-K/AKT) pathway1466
phospholipase A2 680photography of large specimens 47phyllodes tumor, metastases
1395, 1395physical activity, lung cancer risk
960phytosterols, lung cancer 960Pierre–Marry–Bamberger
syndromesee hypertrophicpulmonaryosteoarthropathy(HPOA)
pink puffers, COPD 607placental site trophoblastic
tumor (PSTT),metastases 1399
placental transmogrification 625,626, 626–7, 627
plague 179plasma cell disorders 1337plasmacytic hyperplasia (PH)
787plasmacytoma 1342clinical features 1341differential diagnosis 1341immunohistochemistry 1341pathology 1341, 1341treatment 1341
Plasmodium falciparum 297, 297,300
Plasmodium ovale 297Plasmodium vivax 297plastic bronchitis 635, 635platelet-derived growth factor
(PDGF) 1466–7platelet-derived growth factor
receptor (PDGFR)1433–5
platelets, acute lung injury 354pleomorphic adenoma 1141,
1141–4cell of origin 1141classification 1141clinical features 1141clinicopathologic correlation
1143cytology 1143, 1143differential diagnosis 1143–4electron microscopy 1143genetics 1141histopathology 1141–2, 1142
immunohistochemistry 1143macroscopic pathology 1141metastases 1394molecular findings 1143natural history 1144, 1195pneumocytic
adenomyoepitheliomadifferential diagnosis1145
prognosis 1144, 1195radiographic findings 1141
pleomorphic carcinoma 1187–95,1188
adenocarcinoma 1188b-hCG expression 1190clinical findings 1187CYP1A1 1191–2cytokeratins 1188–9cytology 1188definition 1187differential diagnosis 1192–5EGFR gene mutation 1190–1electron microscopy 1190, 1195EML4-ALK fusion gene 1191epithelial membrane antigen
1188–9histopathology 1187–8, 1189,
1190, 1191immunohistochemistry
1188–90, 1195KRAS gene mutations 1190macroscopic pathology 1187metaplastic 1196molecular findings 1190–2p53 gene mutations 1190p63 gene expression 1190prognosis 1195radiographic findings 1187,
1187surfactant protein A 1189survival 1195thyroid transcription factor 1
1189pleomorphic sarcoma 1197, 1275pleura 30–1asbestos fibers route of entry
1440basement membrane 31biopsy 49black spots 13, 31connective tissue 31elastic layer 31, 31entrapped 59, 60foreign material 1417Kampmeier focus 32mesothelial layer 30–1organization of lung 12–13primary squamous carcinoma
1509reactive eosinophilic vascular
infiltration 1418sarcoidosis 482, 1424
pleural disease 1408–9adenocarcinoma 1494benign 1503–5
asbestos-related 1436–54calcifying fibrous tumor
1429–30connective tissue diseases
1425–6drug-induced lung disease
589–90, 1412, 1426–7endometriosis 1427–8granulomatous 1423–5parasitic 1425rheumatoid arthritis 807, 1425,
1426systemic lupus erythematosus
1425–6Wegener’s granulomatosis
1424, 1424–5see also named diseases and
conditionspleural effusion 1410–4aspergillosis 1412atelectasis 1411–2benign asbestos-associated
1436–7, 1443–4clinical manifestations1443–4
definition 1443differential diagnosis 1444epidemiology 1443etiology 1443lag period from asbestosexposure 1443
pathology 1444congestive heart failure
1410–1eosinophilic 1412, 1414exudates 1410, 1412hepatic cirrhosis 1411infective 1412lactate dehydrogenase 1410lung cancer 977metastatic breast carcinoma
1395mixed connective tissue
disease 827–8natural history 1444nephrotic syndrome 1411pathophysiology 1413–4peritoneal dialysis 1411physiology 1410pleural fluid increase 1410prognosis 1444pulmonary hypoplasia 93radiology 1412–3size 1410systemic lupus erythematosus
1425–6transudates 1410–2treatment 1414tuberculosis 210–11, 211,
217–18, 222, 1412urinothorax 1411
pleural fibromatosis 1443pleural fibrosis 1419–36, 1445,
1446, 1447–8see also diffuse pleural fibrosis
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pleural fluid 1408–9cell content 1409clinical features 1410composition control 1409distribution 1408exchange 1408lymphatic drainage 1408–9mesothelial cells 1408, 1409–10pleural effusion 1410processing 41–2removal 1408–9Starling forces 1409volume 1409volume control 1409
pleural granulomas, calcified 1430pleural lymphoma 1354pleural myxoma 1521pleural patches 13, 31pleural plaques 1436–43apical cap differential
diagnosis 1423asbestos exposure level 1437calcifying fibrous tumor
of the pleura differentialdiagnosis 1430
causes 1439clinical features 1440coronary artery disease
association 1436–7differential diagnosis 1442–3epidemiology 1437–8etiology 1438–9factors affecting production 1437fiber type 1437folded lung differential
diagnosis 1451genetics 1440histopathology 1441–2incidence 1438lag period from asbestos
exposure 1440macroscopic pathology 1441malignancy risk 1443mesothelioma 1443, 1476differential diagnosis 1442–3
non-asbestos causes 1439–40radiography 1437, 1440–1smoking 1439–40
pleural sarcoidosis 482pleural space 1408pleural surface pressure 1408pleural tumors 50adenomatoid 1512melanoma 1513psammoma bodies 1510thymoma 1511, 1512
pleurisy 1412, 1413, 1425Aspergillus 1413fibrosing 1485mixed connective tissue
disease 827–8nonspecific 1420organizing 1487systemic lupus erythematosus
1425
pleuritisbilateral cryptogenic fibrosing
1445chronic fibrinous 1430familial cryptogenic fibrosing
1445idiopathic 1419–20idiopathic lymphocytic 1449rheumatoid arthritis 806systemic lupus erythematosus
815, 1423pleuroparenchymal fibroelastosis
1448pleuropulmonary blastoma
118–23, 1215clinical features 119differential diagnosis 123genetics 122–3histopathology 119–21macroscopic pathology 119pathogenesis 121prognosis 122pulmonary hamartoma
differential diagnosis1227
radiographic abnormalities 119treatment 121Types I–III 120, 121, 121,
122, 123see also pulmonary blastoma
pleuropulmonary fibroelastosis391, 1423, 1448
plexogenic arteriopathy 673–9,676
arterial intimal fibrosis 674–5arteritis 678associated conditions 674cardiac defects 697congenital heart disease
673, 697differential diagnosis 677–8epidemiology 674focal arteritis 676histopathology 674–7, 677, 678medial hyperplasia 674necrotizing arteritis 676plexiform lesion 676risk factors 674Schistosoma infection 684systemic lupus erythematosus
817treatment 678–9vascular lesions 674VEGF1 677
pneumoconiosisbarium 546benign 545–6dental technician’s 545endogenous 58, 693kaolin 538mica 538non-asbestos silicatoses 536–8radiographic classification 521rare earth 544–5talc 536–8
titanium 545–6tungsten carbide 541–3welder’s 547–9see also coal workers’
pneumoconiosis(CWP), mixed dustpneumoconiosis (MDP)/mixed pneumoconiosis,rheumatoidpneumoconiosis (RP)
Pneumocystis jirovecii pneumonia(PCP) 268–72, 271
atypical 269cavitary masses 271classical (typical) 269clinical features 269coin lesions 271diagnosis 269–72differential diagnosis 272epidemiology 268–9extra-pulmonary 269b-D-glucan detection 272granulomatous pneumonitis 466histology 270hypersensitivity pneumonitis
differential diagnosis465–6
immunocompromised patients268–9
interstitial disease 269localized nodular 269lung transplantation 785molecular diagnostics 272necrotizing granulomas 271organism 268pathology 269prognosis 272pulmonary alveolar
proteinosis differentialdiagnosis 397
secondary pneumothorax1415–6
serological tests 271systemic dissemination 271transmission 268treatment 272
pneumocytesdevelopment 4type I 24–5, 25, 355type II 24, 25–6, 25, 26, 355acute lung injury/ARDS346–7
function 25–6hyaline membrane disease105, 106
hyperplasia 348, 380, 916,917
Mallory’s hyaline-likematerial 56, 56
microvilli 25reactive hyperplasia 377
type III (see brush cells)pneumocytic
adenomyoepithelioma1144–5, 1145
clinicopathologic correlation1145
differential diagnosis 1145electron microscopy 1145histopathology 1144immunohistochemistry 1144–5macroscopic pathology 1144,
1144natural history 1145prognosis 1145
pneumonectomy 45–7, 1530pneumoniapleural exudate 1412see also interstitial lung
disease, named typesof pneumonias
pneumonia, bacterialanaerobic bacteria 148, 155–75aspiration 146, 148, 149atypical 147–8, 149bacterial 115–16, 146botryomycosis 176causes 156cavitation of lung 151Chlamydiaceae 175classification 146clinical manifestations 148–9community-acquired 146, 147,
147, 148diagnosis 151, 155early-onset 115–16Enterobacteriaceae 175–6epidemiology 146–8etiology 146–8group B streptococcal
infection 115–16histologic features of bacteria
155host defense 152–4in the immunocompromised
146incidense 146infection events 149–50inflammatory nodules 151inhalation of contaminated
air 149late-onset 116lung shadowing 151management 154microbiological workup 154–5Mycoplasma 176natural history 154nosocomial 146, 148organizing 150pathogenesis 152–4patterns of injury 149pneumococcal 147, 177prognosis 154pseudolipoid 52–3radiologic manifestations
151–2Rickettsiales 179routes of injury 149–51Salmonella 179staining of bacteria 155
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staphylococcal 152, 176Streptococcaceae 176–7see also interstitial pneumonia
pneumonia, fungal 147, 226pneumonia, viral 118, 147, 182–3adenovirus 118, 182–3herpes 117influenza 189measles 183, 193respiratory syncytial virus
118, 191pneumonia hypersensitivity 371pneumonitiscadmium 550CMV 184granulomatous 465, 466mercury 550Mycobacterium avium–
intracellulare complexassociated 219–20
pneumothorax 109–11, 1414–9age factors 1415blebs/bullae 1415, 1418catamenial 1416clinical features 1416–7cysts 1418differential diagnosis 1419eosinophilic infiltration 1418epidemiology 1414, 1414–5genetics 1415, 1416iatrogenic 1416lymphangioleiomyomatosis
1254, 1255Marfan syndrome 428mesothelial proliferation 1417mesothelioma 1469pathology 1417, 1417–8pathophysiology 1418–9primary spontaneous 1414,
1415rheumatoid arthritis 1425risk factors 1415secondary 1414, 1415–6tension 110
podoplanin, mesotheliomadiagnosis 1499
poly-ADP-ribose polymerase(PARP) 1465
polyalveolar lobe 85polyarteritis nodosa 700, 743–5clinical manifestations 744definition 743diagnostic criteria 744differential diagnosis 744–5electron microscopy 744epidemiology 743–4histopathology 744, 745immunohistochemistry 744infection association 743–4laboratory findings 744macroscopic findings 744, 745morphologic stages 744natural history 745pathogenesis 744prognosis 745
pulmonary involvement 743radiographic findings 744
polycyclic aromatichydrocarbons (PAH) 891
polyhydramnios, congenitalperibronchialmyofibroblastic tumor 124
polymyalgia rheumatica,genetics 746
polymyositis 825–7acute fibrinous organizing
pneumonia 827anti-Jo-1 826aspiration pneumonia 827diffuse alveolar damage 826interstitial lung disease 826lung carcinoma 827, 958nonspecific interstitial
pneumonia pattern826, 826
organizing pneumoniapattern 826
paraneoplastic syndrome974–5
pathology 825prognosis 826usual interstitial pneumonia
pattern 826polysplenia syndrome,
arteriovenousmalformations 1261
Pompe disease 425, 425–6clinical features 425electron microscopy 425genetics 425pathology 425prognosis 425–6radiological findings 425treatment 426
popcorn worker’s lung disease 553pores of Kohn 26, 26portal hypertension, plexogenic
arteriopathy 668–70posaconazole, Fusarium
infection treatment 244post-cardiac injury syndrome
1420post-obstructive vasculopathy,
bronchial arteries 665post-transplant
lymphoproliferativedisease (PTLD) 768–9,1345
acute cellular rejectionmorphological mimic 778
classical Hodgkin lymphomatype 788–9
classification 787definition 786diagnosis 787early lesions 787EBV-associated 199, 778,
786–9, 1345immunosuppressive drugs
1348
infectious mononucleosis-like787
monomorphic 788patterns 788polymorphous 787–8risk factors 786treatment 786
Potter’s syndrome, pulmonaryhypoplasia 92
pregnancy, sarcoidosis 490preterm infants 107, 108–9primary ciliary dyskinesia 95–7cilial orientation 96ciliary beat assessment 96diagnosis 95genetics 95investigations 95–6lung disease 96–7ultrastructural studies 96
primary effusion 1355primary effusion lymphoma
1268, 1356clinical features 1355differential diagnosis 1355immunohistochemistry 1355molecular pathology 1355pathology 1355
primary pulmonaryangiosarcoma 1272–5
cell of origin 1272clinical features 1272clinicopathologic correlation
1273differential diagnosis 1273electron microscopy 1273histopathology 1273immunohistochemistry 1273Kaposi’s sarcoma differential
diagnosis 1272macroscopic pathology 1273molecular findings 1273natural history 1273prognosis 1273radiographic findings 1272–3treatment 1273
primary pulmonarychondrosarcoma 1238,1238–9
differential diagnosis 1238–9pathology 1238prognosis 1239
primary pulmonary glomustumors 1167, 1247–9
cell of origin 1247classification 1247clinical features 1248clinicopathologic correlation
1249cytology 1248differential diagnosis 1249electron microscopy 1249histopathology 1248immunohistochemistry
1248–9macroscopic pathology 1248
malignant 1248molecular findings 1249radiographic findings 1248succinated dehydrogenase
missense mutation 1249primary pulmonary leiomyoma/
leiomyosarcoma 1242–3primary pulmonary lipoma
1231–3age factors 1231cell of origin 1231classification 1231clinical features 1231clinopathologic correlation
1232cytology 1232differential diagnosis 1233electron microscopy 1232genetics 1231histopathology 1231immunohistochemistry 1232macroscopic pathology 1231molecular findings 1232natural history 1233prognosis 1233radiographic features 1231
primary pulmonary liposarcoma1233–4, 1521
cell of origin 1233classification 1233clinical features 1233clinicopathologic correlation
1234dedifferentiated 1233differential diagnosis 1234electron microscopy 1233genetics 1233histopathology 1233immunohistochemistry 1233macroscopic pathology 1233molecular findings 1234myxoid 1233natural history 1234pleomorphic 1233prognosis 1234radiographic findings 1233
primary pulmonary malignantmelanoma 1286–8, 1401
cell of origin 1286classification 1286clinical features 1287clinicopathologic correlation
1288cytology 1287differential diagnosis 1288electron microscopy 1287genetics 1286histopathology 1287immunohistochemistry 1287macroscopic pathology 1287molecular findings 1287natural history 1288pagetoid spread 1287prognosis 1288radiographic findings 1287
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primary pulmonary meningioma1230–1
cell of origin 1230classification 1230clinical features 1230clinicopathological correlation
1230cytology 1230differential diagnosis 1230–1electron microscopy 1230histopathology 1230immunohistochemistry 1230macroscopic pathology 1230minute pulmonary
meningothelial-likenodule differentialdiagnosis 1229
natural history 1231prognosis 1231radiographic findings 1230
primary pulmonary osteogenicsarcoma 1235–6
classification 1235clinical features 1235clinicopathologic correlation
1235CXCR4 chemokine receptor
1235differential diagnosis 1235–6histopathology 1235immunohistochemistry 1235macroscopic pathology 1235molecular findings 1235natural history 1236P-glycoprotein 1235prognosis 1236radiographic findings 1235
primitive neuroectodermaltumor (PNET) 1170–1,1171, 1249, 1519–20
probe method of dissection 49progenitor cells, lung
development 7progressive massive fibrosis
(PMF) 533, 534, 535, 535coal workers’ pneumoconiosis
535complicated 534differential diagnosis 535–6rounded atelectasis 1451talcosis 537
prostate adenocarcinoma,metastases 1399, 1400
protein gene product 9.5(PGP 9.5) 21, 1164–5
proteinase 3 622, 711Proteus, pneumonia 116Proteus mirabilis pneumonia 175protozoal infections 288, 289–307amebiasis 291–5babesiosis 300Balantidium coli 307cryptosporidiosis 305–7Cyclospora 307leishmaniasis 289–91
Lophomonas 307malaria 297–300microsporidiosis 304–5toxoplasmosis 301–4Trichomonas 307trypanosomiasis 295–7
psammoma bodies 1510, 1526Pseudallescheria boydii 241, 242pseudoangiosarcomatous
carcinoma 1193pseudoepitheliomatous
adenocarcinoma 1509pseudolymphoma see nodular
lymphoid hyperplasiapseudomesotheliomatous
adenocarcinoma 1065Pseudomonas 116, 116Pseudomonas aeruginosa 162, 176cystic fibrosis 99, 100
Pseudomonas cepaciasee Burkholderia cepacia
Pseudomonas fluorescens 459pseudopneumoconiosis 693psittacosis 148, 175pulmonary adenocarcinogenesis
924see also peripheral lung
adenocarcinogenesispulmonary agenesis 74–5bilateral 74, 75lobar 75unilateral 74–5
pulmonary alveolar microlithiasis394, 394, 395
diagnosis 394genetics 394natural history 394pathology 394prognosis 394radiological findings 394
pulmonary alveolar proteinosis(PAP) 394–7, 396, 397
childhood/infant 395clinical course 397clinical features 395–6diagnosis 396, 397differential diagnosis 397drug-induced lung disease 589etiology 394–5GM-CSF 395, 397idiopathic 395opportunistic infections 396–7pathology 396–7prognosis 397radiological findings 396secondary 395type II 397
pulmonary arterial tension,HIV-related 201–2
pulmonary arterial trunk 11, 32pulmonary arteries 28–9adventitia 28, 29changes 666, 689
aging 32anatomy 663–4
concentric laminar intimalfibrosis 675
development 4elastic 28–9intima/media 28medial hyperplasia 675muscular 28, 29, 29newly formed muscular media
675occlusion with
thromboembolism/thrombosis 680
organization 11stenosis 72supernumerary arterial
branches 663, 664–5, 666walls 28
pulmonary arterioles 28, 29–30,663–4
pulmonary arteriovenousmalformation 1262
pulmonary artery aneurysms,Behçet syndrome 831
pulmonary artery sarcoma1278–81
cell of origin 1279classification 1279clinical features 1279clinopathologic correlation
1281differential diagnosis 1281electron microscopy 1279genetics 1279histopathology 1279immunohistochemistry 1279macroscopic pathology 1279molecular findings 1281natural history 1281prognosis 1281radiographic findings 1279treatment 1281
pulmonary blastoma 1170, 1187,1205–16
age factors 1205blastomatoid carcinosarcoma
differential diagnosis1203, 1214–5
carcinosarcoma differentialdiagnosis 1199–200, 1204
b-catenin gene mutation1212–3
cell of origin 1207clinical features 1203, 1206,
1207cytology 1210, 1212, 1213definition 1206–7differential diagnosis 1211,
1214–5electron microscopy 1211–2epidemiology 1207epithelial cells 1210glandular cells 1209histopathology 1209, 1209,
1210historical overview 1205–6
immunohistochemistry1210–1, 1214, 1215
macroscopic pathology 1208–9,1208
melanocytic differentiation 1213mesenchymal cells 1210, 1211mesenchymal component
1209metastases 1209molecular findings 1212–3morular formation 1209,
1210–1, 1211–2natural history 1215–6p53 gene mutations 1213pathological features 1203,
1206pleomorphic adenoma
differential diagnosis1143–4
prognosis 1215–6radiographic findings 1207,
1208smoking 1207stromal cells 1212studies 1205–6treatment 1216Wnt signaling pathway
activation 1212see also pleuropulmonary
blastomapulmonary calcification 392–3dystrophic 392metastatic 392–3pathology 393treatment 393
pulmonary capillaries 29–30, 665pulmonary capillary
hemangiomatosis (PCH)695
associated conditions 692capillary proliferation 693clinical features 691differential diagnosis 693epidemiology 691hemosiderin deposition 693histopathology 693intimal fibrosis 693medial hyperplasia 693pulmonary hypertension
691–3radiologic features 692–3treatment 691vascular lesions 696
pulmonary chondroma 1237–8Carney’s triad 1237cell of origin 1237classification 1237clinical features 1237differential diagnosis 1237genetics 1237histopathology 1237macroscopic pathology 1237natural history 1238prognosis 1238radiographic findings 1237
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pulmonary circulatory system10–11, 663, 665–6
pulmonary cystic disease 75–82acinar dysplasia 82age 76bronchogenic cysts 77–8congenital adenomatoid
malformations 78–82diagnosis 76–7diagnostic criteria 76spectrum 76
pulmonary diffusion, alveolarvolume relationship 7
pulmonary ectopic deciduosis 879pulmonary edema 568–9pulmonary embolism 153, 684chronic thromboembolic
pulmonary hypertensionrisk 679
foreign body 686malignancy 684non-thrombotic causes 684–6pulmonary artery sarcoma
1281radiological findings 667tumor emboli 1389, 1390
pulmonary eosinophiliasyndromes 308, 309
pulmonary epithelialhemangioendothelioma(EHE) 1263–8
pulmonary fibrosis 349coal dust-induced 532–3diffuse interstitial 536Hermansky–Pudlak syndrome
419, 421idiopathic 608mixed dust pneumoconiosis
532paraquat toxicity 598pediatric lung transplantation
768see also progressive massive
fibrosis (PMF)pulmonary glial nodules 90pulmonary glomangiosarcoma
1248, 1249pulmonary hamartoma 1224–7age factors 1224angiomyolipoma differential
diagnosis 1256cell of origin 1224classification 1224clinical features 1224clinicopathologic correlation
1227cytology 1225, 1227diagnosis 1225differential diagnosis 1227electron microscopy 1225endobronchial 1224–5genetics 1224histopathology 1225macroscopic pathology
1224–5, 1226
natural history 1227pleomorphic adenoma
differential diagnosis1143–4
primary pulmonary lipomadifferential diagnosis1233
prognosis 1227pulmonary chondroma
differential diagnosis1237
radiographic features 1224,1225
pulmonary hemorrhage 111–12ANCA 742causes 742differential diagnosis 742–3drug-induced lung disease
589, 742prognosis 743pulmonary endometriosis
differential diagnosis 879pulmonary–renal syndromes
742treatment 743
pulmonary hemorrhagesyndromes 740–5, 740
antiphospholipid syndrome741, 742
pulmonary hemosiderosis,idiopathic 742
pulmonary hyalinizinggranuloma (PHG)872–4, 873
associated diseases 872–3clinical features 872–3clinicopathological correlation
874differential diagnosis 874electron microscopy 874epidemiology 872–3etiology 872–3histopathology 873–4, 874macroscopic pathology 873,
873natural history 874pathogenesis 874prognosis 874radiologic features 873serologic associations 873
pulmonary hyperplasia 86–7, 87,90, 1242
pulmonary hypertension 662–3alveolar capillary dysplasia 89animal models 668antiphospholipid syndrome 820appetite suppressants 670associated conditions 661BMPR2 668–70bronchopulmonary dysplasia
108chronic myeloproliferative
disorders 684–6chronic thromboembolic
679–86
classification 662, 662–3, 673congenital heart disease 667–8,
693–7congestive vasculopathy 667,
683–4, 689–91connective tissue disease 392,
697–8, 804COPD 621CREST syndrome 697–8, 822cystic fibrosis 99, 103definition 661drug-induced lung disease
589endothelin-1 392Gaucher disease 410, 412, 414,
698genetics 668histopathologic patterns 672–91,
822hypoxic arteriopathy 686–9idiopathic 661inflammation 670interstitial lung disease 392,
698–700intimal fibrosis in systemic
sclerosis 697Langerhans’ cell histiocytosis
1351leukemia 684–6mechanisms of development
669mixed connective tissue
disease 827non-thrombotic embolic
684–6pathogenesis 668plexogenic arteriopathy 673prognosis 822pulmonary arterioles 664pulmonary capillary
hemangiomatosis 691–3pulmonary tumor thrombotic
microangiopathy 1376pulmonary veno-occlusive
disease 667, 691–3radiological findings 666–8,
667Raynaud’s phenomenon 825rheumatoid arthritis 813risk factors 661sarcoidosis association 392, 492Schistosoma infection 684scleroderma 822, 822serotonin 670sickle cell disease 680Sjögren’s syndrome 825smoking-related disease 392systemic lupus erythematosus
670, 697, 698, 815, 817systemic sclerosis 392, 667,
697–8T cells 675thrombotic arteriopathy
679–86tissue specimen handling 663
vascular disease patterns 673vascular pathology 661vascular remodeling 392,
621, 668vasculitis 700see also idiopathic pulmonary
arterial hypertension(IPAH), plexogenicarteriopathy
pulmonary hypoperfusion696
pulmonary hypoplasia 91–3,93, 94
autopsy 92–3classification 92diagnosis 92–3diaphragmatic hernia 98elastin absence 93fetal breathing impairment 91histology 93idiopathic 92inadequate thoracic volume 91lung:bodyweight ratio 92–3morbidity/mortality 93oligohydramnios 91–2, 93primary 92radial alveolar count 93respiratory distress syndrome
92pulmonary infarction 683–4, 685,
690–1pulmonary interstitium 27–30see also interstitial entries
pulmonary lobule 10pulmonary lymphangio-
leiomyomatosis (PLAM)see lymphangio-leiomyomatosis
pulmonary lymphangiticcarcinomatosis (PLC)1382–4
differential diagnosis 1384pathology 1383–4pathways 1382radiographic findings 1383signs/symptoms 1382–3
pulmonary lymphoepithelioma-like carcinomas (PLELC)956
pulmonary malignant nervesheath tumor 1239
pulmonary mycotoxicosis 439pulmonary neuroendocrine
cells (PNCs) 19–22, 1151,1172
function 20–1hyperplasia 1172, 1173immunohistochemistry 1175neurosecretory vesicle 21–2proliferating 1174, 1175,
1177pulmonary nodular disease
184, 1393see also nodular lymphoid
hyperplasia
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pulmonary ossification 55, 392,393, 393
pulmonary papillomatosis 851pulmonary parenchymal diseaseBehçet’s syndrome 750beryllium-induced 540carcinogenesis and scar cancer
theory 910diffuse 366, 366inflammatory bowel disease 834sarcoidosis 478, 480
pulmonary parenchymal tears,Ehlers–Danlos syndrome430–1
pulmonary preinvasive disease889–929
angiogenesis 905–6apoptosis 903basal cell hyperplasia 892–3bronchial lesions 902–9bronchioalveolar lesions 910–11carcinogenesis 909–10, 921–2,
928–9cell immortalization 906genetic factors 929genomic instability 907–8hyperproliferation 903mitosis 903molecular biology 902–9mucus cell hyperplasia 892p53 protein 903–4peripheral lung
adenocarcinogenesis909–19, 921–2
peripheral lung epithelialcarcinogenesis 909–10
progression 908–9, 929sputum atypia 908squamous dysplasia/
carcinoma-in-situ891, 892
squamous metaplasia 891, 892,893–4
transcription factors 906tumor suppressor genes 903–4,
906tyrosine kinase signaling
pathways 905see also atypical adenomatous
hyperplasia (AAH),squamous dysplasia/carcinoma-in-situ(SD/CIS)
pulmonary pseudoisomerism68, 69
pulmonary schwannoma 1239pulmonary sequestration 82–4bronchopulmonary foregut
malformation 85elastic tissue 84extralobar 82–3, 82intralobar 82, 83–4, 84diagnosis 83histology 84management 83–4
isolated systemic arterialsupply 85
mucus retention 84pulmonary teratoma 1285–6cell of origin 1285classification 1285clinical features 1285clinicopathologic correlation
1286differential diagnosis 1286genetics 1285histopathology 1285–6immunohistochemistry 1286macroscopic pathology 1285malignant 1285–6natural history 1286prognosis 1286radiographic features 1285
pulmonary trunk 11pulmonary tumor thrombotic
microangiopathy(PTTM) 1376
pulmonary vascular disease686, 813, 815
pulmonary vasculatureanastomotic complications in
lung transplantation 772–3anatomy 663–6, 664, 665, 666bacterial infection route 150–1
pulmonary vein(s) 11, 30, 30,90, 665
pulmonary vein sarcoma 1243–4cell of origin 1243classification 1243clinical features 1243clinicopathologic correlation
1244cytology 1244differential diagnosis 1244electron microscopy 1244genetics 1243histopathology 1243immunohistochemistry 1244macroscopic pathology 1243molecular findings 1244natural history 1244prognosis 1244radiography 1243
pulmonary veno-occlusivedisease (PVOD) 694
associated conditions 692autoimmune disease
association 691chemotherapy-induced 691clinical features 691connective tissue disease
association 691differential diagnosis 693epidemiology 691hemosiderin deposition 693histopathology 693intimal fibrosis 693medial hyperplasia 693pulmonary hypertension
667, 691–3
radiation therapy-induced 691radiologic features 692–3treatment 691vascular lesions 696
pulmonary venules 11pulmonary–renal syndromes 742pyoderma gangrenosum 832,
832–3, 833pyothorax-associated lymphoma
1357clinical features 1356differential diagnosis 1357EBV association 1356immunohistochemistry 1356molecular pathology 1356pathology 1356, 1356primary effusion lymphoma
differential diagnosis1356
prognosis 1356treatment 1356
Q fever 179quercetin 959
radial alveolar count 4, 93radiation pneumonitis 593–4acute 594chronic 594epidemiology 593–4histopathology 594, 594pathogenesis 593with subsequent
chemotherapy 594radiation recall pneumonitis 594radiation therapy 594–5, 595,
691, 1461–2radiation toxicity 593–5radiofrequency ablation 595radon, lung cancer 951RANTES 748, 1412rapamycin/rapamycin analog
toxicity 592rapidly-adapting stretch
receptors (RARs) 12rare earth pneumoconiosis
544–5, 545Raynaud’s phenomenon 698, 825RB1 gene mutations 960reactive nitrogen species (RNS)
1464–5reactive oxygen species (ROS)
157, 1464–5refractory ceramic fibers (RCF)
518, 550, 1439, 1445, 1462regional alveolar damage 382Reid index 614relapsing polychondritis 830,
830–1renal cell carcinoma 1258, 1510metastases 1380, 1397, 1397
Rendu–Osler–Weber diseasesee hereditaryhemorrhagictelangiectasia
respiratory bronchiolitis (RB)385–8
clinical presentation 385diagnostic criteria 388differential diagnosis 386–7histopathology 385–6lung transplantation 790prognosis 388radiological findings 385
respiratory bronchiolitis-associated interstitiallung disease (RB-ILD)367, 385–8
clinical presentation 385diagnostic criteria 388differential diagnosis 386–7histopathology 385–6prognosis 388radiological findings 385
respiratory distress syndrome103–6
air leaks 109, 111diagnostic criteria 104host reaction 104–5incidence 104natural history 104pathology 104pulmonary hemorrhage 111pulmonary hypoplasia 92risk factors 104surfactant therapy 105see also hyaline membrane
diseaserespiratory epithelium 14–16, 153respiratory papillomatosis 850respiratory pathways, collateral
26respiratory syncytial virus 117,
182–3, 191–2bronchiolitis 191, 191diffuse alveolar damage 191multinucleated epithelial
cells 191pathology 191pneumonia 118, 191
respiratory tract cells 14, 15–23,24–8, 30
resveratrol 958retinoblastoma 960pathway 904–5
retinoblastoma (Rb) genemutations 960, 1103, 1115
retinoic acid receptor (RAR) 906retinopathy, paraneoplastic
syndrome 974retroperitoneal fibrosis 1445RGS17 (regulator of G-protein 17)
gene 965rhabdomyomatous hyperplasia
90, 1242rhabdomyosarcomaalveolar 123, 1514–5embryonal 123pulmonary 123–4, 1242
rheumatoid arthritis 806–14
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airway disease 811–13amyloidosis 814, 814, 1337,
1338bronchiectasis 813, 813Caplan’s syndrome 808chronic bronchiolitis 813, 813diffuse alveolar damage
pattern 811, 811diffuse alveolar hemorrhage
813empyema 1425eosinophilic pneumonia 814,
814follicular bronchiolitis 812–13interstitial lung disease 808–9lung cancer 814lymphocytic interstitial
pneumonia pattern 811,811
lymphoid hyperplasia 812–13lymphoid proliferation 1317–8lymphoproliferative disorders
814methotrexate-associated
diffuse large B-celllymphoma 814
non-specific interstitialpneumonia pattern809, 810
obliterative bronchiolitis811–12, 812
organizing pneumonia pattern809, 810
pathology 807, 810pleural disease 807, 1425, 1426pleuritis 806pneumothorax 1425pulmonary hypertension 813usual interstitial pneumonia
pattern 809vascular disease 813vasculitis 814
rheumatoid nodules 807–8, 807,808
cavitary 807pathology 807, 808prognosis 808tuberculosis differential
diagnosis 222Wegener’s granulomatosis
differential diagnosis 729rheumatoid pneumoconiosis
(RP) 531, 531, 808, 808rhinosinusitis, lung cancer
risk 957rhinovirus 184Rhodococcus equi pneumonia
173, 178–9Rickettsia conorii pneumonia 179Rickettsia rickettsii pneumonia
173, 174, 179Rickettsiales pneumonia 179right-to-left shunting,
arteriovenousmalformations 1261
right ventricular dysfunction621–2, 697
rituximab toxicity 593river blindness 308rock wool 550Rocky Mountain spotted fever 179Roget cells see pericytesRosai-Dorfman disease 412,
1354, 1354rounded atelectasis 1448–51asbestos count 1451differential diagnosis 1451
rutile 546
S-100 antigen 1165S sign of Golden, squamous
cell carcinoma 1094sagittal slicing 47salivary gland carcinoma,
metastases 1394salivary gland neoplasms
1127–48acinic cell carcinoma 1138–41adenoid cystic carcinoma
1107–8, 1133–6epithelial–myoepithelial
carcinoma 1136–8mucus gland adenoma 1132–3,
1146–8oncocytoma 1148pleomorphic adenoma 1141–4pneumocytic
adenomyoepithelioma1144–5
see also mucoepidermoidcarcinoma
Salmonella pneumonia 174, 179Sanfilippo syndrome 422sarcoid granulomas 464, 481,
482, 483, 483pleural 1424
sarcoidal inclusions 56sarcoidosis 475airway involvement 493angiotensin-converting
enzyme serum levels 489antigen presentation 489antigens 476aspergilloma 482asteroid bodies 485, 485autoimmune disease
association 490berylliosis differential
diagnosis 541biopsy 488bronchiolar 484bronchoalveolar lavage 489calcium oxalate crystals 486cavitary 493classification 479clinical associations 488, 489clinical presentation 478, 492common variable
immunodeficiency 490cutaneous anergy 490
cyst formation 484cytology 487, 487definition 475diagnosis 487differential diagnosis 491diffuse pleural fibrosis
differential diagnosis1447–8
electron microscopy 487end-stage 484environmental triggers 477epidemiology 475epithelioid cells 489ethnic differences 476, 476etiology 476, 477, 477genetics 476geographical distribution 476granulomas 464, 481, 483, 483,
484, 491Hamazaki–Wesenberg bodies
486, 486histopathology 481, 482, 700historical aspects 475HIV infection 490HLA association studies
476, 477hypersensitivity pneumonitis
differential diagnosis 464immune reconstitution
inflammatory syndrome490
immunopathogenesis 489inclusions 485infections 477, 488, 491interferon therapy
complication 490, 492intrathoracic adenopathy 478Kveim–Siltzbach test 489laboratory findings 489lung transplantation recurrent
disease 793–5lymph node involvement 480lymphangitic distribution
482, 488macroscopic pathology 479,
480, 481, 483malignancy association 490natural history 492necrotizing sarcoid
granulomatosis 494, 1424nodular 479, 493, 494, 495pleural 482, 1424pleural effusions 493pregnancy 490prognosis 492pulmonary function tests 478pulmonary hypertension
association 392, 492pulmonary parenchymal
disease 478, 480radiographic findings 478,
479, 480remission rates 492Schaumann bodies 485, 486secondary pneumothorax 1416
smoking 477staging system 480symptoms 478T helper cells 489, 490transbronchial lung biopsy 488transbronchial needle
aspiration biopsy 489treatment 493tuberculosis differential
diagnosis 221variants 493vascular involvement 485Wegener’s granulomatosis
differential diagnosis 729see also necrotizing sarcoid
granulomatosissarcoma 1192metastases 1247, 1400–1see also osteosarcoma, primary
pulmonary osteogenicsarcoma, pulmonaryartery sarcoma, synovialsarcoma
sarcomatoid carcinoma 1186–216classification 1186cytokeratin 7 expression 1020cytology 1194epithelial–mesenchymal
transition 1186–7giant cell sarcoma 1195–7histogenesis 1186–7incidence 1186inflammatory 1193–4, 1193mesothelioma differential
diagnosis 1516–7pleomorphic adenoma 1141–4pleomorphic carcinoma
differential diagnosis1192–4
primary pulmonaryangiosarcoma differentialdiagnosis 1273
primary pulmonary osteogenicsarcoma differentialdiagnosis 1236
sarcomatoid mesotheliomadifferential diagnosis1194–5
spindle cell carcinoma1187–95
thyroid transcription factor 1expression 1018, 1020
transdifferentiation spectrum1187
see also pleuropulmonaryblastoma, pulmonaryblastoma
sarcomatoid carcinosarcoma1516
sarcomatoid mesothelioma1476–7
cadherins 1503calretinin sensitivity 1496–7,
1502–3cytokeratin 5/6 1502
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sarcomatoid mesothelioma(cont.)cytokeratin-negative 1496HBME-1 1503histologic variants 1490immunohistochemistry 1500–3primary pulmonary
chondrosarcomadifferential diagnosis1238–9
prognosis 1529sarcomatoid carcinoma
differential diagnosis1194–5
synovial sarcoma differentialdiagnosis 1283
vimentin 1502Wilms’ tumor gene product
1503Sauropus androgynus ingestion
642–3, 643scar cancer theory 910scars/scarring 54Scedosporium infection 238, 241–3clinical features 242–3diagnosis 243epidemiology 241–2incidence 228invasive disease 243mortality 243organisms 241pathology 243prognosis 243treatment 243
Schaumann bodies 55, 56, 541sarcoidosis 485, 486
Scheie syndrome 422Schistosoma (schistosomiasis)
322–6acute 324chronic 325clinical features 324diagnosis 325–6egg 323, 324epidemiology 322–4life cycle 323necrotizing granulomas 325organism 323–4, 324pathology 325plexogenic arteriopathy 684pulmonary hypertension 684pulmonary vascular disease 686radiographic appearance 325treatment 326
scleroderma see systemicsclerosis
sclerosing hemangioma 864–72alveolar adenoma differential
diagnosis 864cell of origin 864–5cell types 868classification 864–5, 867clinical features 865clinicopathological correlation
871–2
cuboidal cells 869, 870cystic pattern 866cytology 869–70, 869, 870differential diagnosis 872electron microscopy 870–1etiology 864–5genetics 865histopathology 866–9, 868immunohistochemistry 870, 871lung adenocarcinoma
differential diagnosis 1065macroscopic pathology 865–6,
865, 866metastases 869molecular findings 871multiple 866, 867natural history 872neuroendocrine markers 870neuroendocrine proliferations
866–7papillary adenoma differential
diagnosis 861papillary pattern 866, 869pathogenesis 864–5prognosis 872radiographic findings 865sex steroid hormone receptor
expression 870solid pattern 866, 869stromal metaplasia 868thyroid transcription factor 1
expression 1019scrub typhus 179sea-blue histiocytes 416–17secretoglobin 1a1 (Scgb1a1) 7sectioning techniques 46–7segmentectomy 45–7semaphorins 905senile lung 623senile pulmonary amyloid (SSA)
32, 56sensory receptors 12sepsis, hematogenous spreadCandida 265pneumonia-causing organisms
150, 151–2septic emboli 150, 151–2seromucinous glands 15, 16, 23serotonin, pulmonary
hypertension 670serous borderline tumor of
paratestis 1473serous cells 18–19serous papillary carcinoma of the
ovary 1512SERPINA1 gene mutations
606, 619Serratia marcescens pneumonia
160, 175serum mesothelin-family
proteins (SMRP) 1454severe acute respiratory syndrome
(SARS) 182, 190sex cord stromal tumors,
metastases 1398
Sézary syndrome 1346Shp2 tyrosine protein
phosphatase 6shrinking lung syndrome 819shrinking pleuritis with rounded
atelectasis see folded lungsialomucins, cell-associated
1409sickle cell disease 681acute chest syndrome 680, 681chronic lung disease 680hypoxia 680pulmonary hypertension 680
siderosilicosis 544silicabiologic activity 528exposure 528mineralogy 528occupations causing exposure
528particle size 528tissue injury mechanisms 528
silicates 528, 536, 538, 1445silicatoses, non-asbestos 536–40silicon carbide pneumoconiosis
544, 545silicoproteinosis, acute (ASP)
530–1, 531silicosis 528alveolar lipoproteinosis 530–1bronchogenic carcinoma
association 531–2clinical features 528complicated 529conglomerate 529diagnosis 529emphysema 530endobronchial 633–4extrathoracic lesions 530fibrosis 529immune dysfunction 531–2latency period for
development 528Mycobacterium tuberculosis
infection 529nodular 529, 529, 530, 530pathogenesis 528pathologic features 529–31radiologic features 528–9, 529rounded atelectasis 1451
silicotic lung disease 528–32silo-unloader’s syndrome 439simian virus 40, 1463
mesothelioma 1462–3single gene polymorphisms,
lung cancer risk 960–3sirolimus toxicity 592, 791, 1255Sjögren syndrome 823–5amyloidosis 1338, 1339autoantibodies 823, 825bronchi/bronchioles 824–5chronic bronchiolitis 825diagnosis 823interstitial lung disease
823–4
lymphocytic interstitialpneumonia 823–4,1319, 1320
lymphoid hyperplasia 824, 825lymphoid proliferation 1317–8marginal zone B-cell
lymphoma 825nodular lymphoid hyperplasia
825non-Hodgkin’s lymphoma 825nonspecific interstitial
pneumonia pattern823, 824
organizing pneumonia pattern824
pathology 823primary 823pulmonary hypertension 825secondary 823usual interstitial pneumonia
pattern 824slab technique 46–7SLC34A2 gene mutation 394sleeping sickness
see Trypanosoma brucei(African trypanosomiasis)
sleeve lobectomy 46, 46sling left pulmonary artery 69slowly-adapting stretch receptors
(SARs) 12small airway diseases 636–48, 637classification 637–8clinical features 636–7definition 636inflammatory bowel disease
833–4see also bronchiolitis, diffuse
panbronchiolitis (DPB),follicular bronchiolitis,peribronchiolarmetaplasia
small cell carcinoma 1153extra-pulmonary 1020, 1022
small cell lung carcinoma(SCLC) 889, 909, 949,1162
Azzopardi phenomenon1162–3, 1163
basaloid carcinoma differentialdiagnosis 1118
basaloid squamous cellcarcinoma differentialdiagnosis 1107–8
carcinoid tumor differentialdiagnosis 1169
classification 1151–2clinical features 1153combined 1093, 1164crush phenomenon 1162–3,
1167cytology 978, 1162, 1163–4,
1163, 1165dense core vesicles 1151differential diagnosis 1167–8dissemination 1153
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electron microscopy 1166epidemiology 1153genetics 1166–7histopathology 1162–4incidence 949intra-pulmonary thymoma
differential diagnosis1285
large cell neuroendocrinecarcinoma differentialdiagnosis 1168–9, 1169
lymphoid infiltrate differentialdiagnosis 1028
macroscopic pathology 1156,1156–7, 1162
marginal zone lymphomadifferential diagnosis1328–9
metastases 1153natural history 1169neuroendocrine markers 1027non-endocrine component
1164paraneoplastic effects 1153prognosis 1169pulmonary blastoma
differential diagnosis1215
radiographic findings 1156,1156
small cell variant of squamouscell carcinoma differentialdiagnosis 1106–7, 1029
squamous cell carcinomacombination 1093differential diagnosis 1031
staging 1169subtypes 1151–2thyroid transcription factor 1
expression 1016, 1018,1022
TNM classification 1012small specimen histological
processing 42–3description 42fixatives 42handling 42identification 42media 42molecular testing 43, 50–1pathological finding
correlation with clinicalfindings 42–3
sample collection 42tissue amounts 43
small vessel remodeling inthrombotic arteriopathy683
small vessel vasculitis 622smokingacute eosinophilic pneumonia
579asbestos exposure and lung
cancer 525, 526, 953asbestosis 520, 525, 1439–40
atypical adenomatoushyperplasia association921, 926–7
bidi composition 950bronchial carcinogenesis 891bronchiolitis 644bronchus-associated lymphoid
tissue 15carcinogenic effects 900carcinogens 950, 951carcinosarcoma 1198cessation 950chromosome 3p changes 907cigarette composition 950coal dust exposure 536COPD 609–11emphysema 620, 621epidemiology 947giant cell sarcoma 1196goblet cell metaplasia 565hypersensitivity pneumonitis 449irritant effects 900Langerhans’ cell histiocytosis
1349, 1351lesions in lung transplantation
790, 791lung adenocarcinoma 1066lung cancer association 890–1,
946, 947–8, 950–1macrophage production
27, 385p16 gene 907passive 950pleural plaques 1439–40prevalence 929pulmonary blastoma 1207pulmonary hypertension 392rates 946sarcoidosis 477squamous cell carcinoma 1094squamous cell papilloma
association 850squamous dysplasia/
carcinoma-in-situ 891, 900squamous metaplasia 893–4see also respiratory
bronchiolitis (RB),respiratory bronchiolitis-associated interstitial lungdisease (RB-ILD)
smoking-related interstitial lungdisease 385
smooth muscle 23hyperplasia 54–5, 55
smudge cells, adenovirus 194, 194soft tissue sarcoma, metastases
1400solid fuel use, lung carcinoma 946solitary fibrous tumor of the
pleura 1429–36benign area transition to
malignant area 1434calcifying fibrous tumor
of the pleura differentialdiagnosis 1429–30
cell of origin 1430–1classification 1436clinical features 1431clinicopathological correlation
1435–6cytology 1433differential diagnosis 1435electron microscopy 1433genetics 1431hemangiopericytoma-like
pattern 1433histopathology 1432hypertrophic pulmonary
osteoarthropathy 1431hypoglycemia 1431immunohistochemistry 1433,
1435incidence 1430keloid-type area 1433macroscopic pathology 1431malignant potential 1434mesothelioma differential
diagnosis 1518molecular findings 1433–5natural history 1436paraneoplastic syndromes 1431patternless pattern 1433prognosis 1436pseudorosette area 1434radiology 1431treatment 1436
Sparganum mansoni(sparganosis) 334–5
specimen handling 41–62ancillary studies 49–51autopsy 45–7bronchoplastic resection 45–7cytology specimen processing
41–2electron microscopy 50histochemical stains 49immunohistochemistry 49–50incidental lesions 53, 53–9large surgical pathology
specimen processing43–9
lung carcinoma large specimenevaluation 47–9
molecular techniques 43, 50–1pneumonectomy 45–7segmentectomy 45–7simple lobectomy 45–7small specimen histological
processing 42–3see also biopsy
sphingolipidoses 409sphingomyelin 414, 416sphingosine-1-phosphate (S1P) 18spindle cell carcinoma 1187–95carcinosarcoma differential
diagnosis 1204clinical findings 1187cytology 1188definition 1187differential diagnosis 1192–5
electron microscopy 1190histopathology 1188immunohistochemistry
1188–90macroscopic pathology 1187molecular findings 1190–2natural history 1195prognosis 1195radiographic findings 1187
Splendore-Hoeppli 233, 273, 310,324, 325
spindle cell sarcoma 864, 1517–8sponge artefact, biopsy 52, 53Sporothrix schenckii
(sporotrichosis) 272–4, 273clinical features 272culture 274diagnosis 273–4differential diagnosis 274epidemiology 272organism 272pathology 272–3prognosis 274serological tests 274South American blastomycosis
differential diagnosis 264systemic 272treatment 274
sputumatypia 908cytology processing 41–2microbiological workup 154
squamous cell(s), cytologicalatypia 891–2
squamous cell carcinoma 949,1093–108
aberrant methylation of CpGislands 1103–4
acantholytic 1193age factors 1094alveolar filling type 1105,
1097–8amyloid-like stroma 1101atypical carcinoid tumor
differential diagnosis1167
basaloid variant 1107–8, 1108,1118
carcinosarcoma 1198malignant spindle cell stromalcomponent 1188, 1192
small cell lung carcinomadifferential diagnosis1167–8
cavitation 1094, 1095, 1105cell of origin 1093central tumors 1095–6, 1097,
1098classification 1093clear cell 1106, 1106, 1107clinical features 1094clinicopathologic correlation
1104CT scanning 1095cystic change 1098
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squamous cell carcinoma (cont.)cytology 1100–2, 1102, 1103desmosomes 1103diagnosis 1104differential diagnosis 1104–5electron microscopy 1103epidermal lysosomes 1103epigenetic modifications
1103–4gender 1094gene deletions 1093–4genetics 1093–4granular cell tumor differential
diagnosis 1242high grade 1099histone modification 1104histopathology 1106, 1096–9,
1097, 1098, 1099human papilloma virus
association 906, 1098–9immunohistochemistry 1101,
1103, 1099incidence 889, 949, 1093intrathoracic spread 1094keratin gene expression 1104keratinizing 1101lung adenocarcinoma
differential diagnosis1027, 1029
macroscopic pathology1095–6, 1096
metastases 1094microRNAs 1104, 1105molecular findings 1103–4morpheaform invasion 1101morphologic variants 1099Napsin A positivity 1023natural history 1105non-keratinizing 1101–2, 1102occult of bronchus 1094Odland bodies 1103papillary 1105–6, 1105, 1106paraneoplastic syndromes 1094pathogenesis 1093peripheral lung 1105, 1094–5,
1096, 1096, 1097–8,1099, 1100
PET-CT scanning 1095primary of pleura 1509prognosis 1105pseudoangiomatous 1273pseudoglandular 1101radiographic findings 896,
1094–5, 1095S sign of Golden 1094small cell lung carcinoma
1031, 1093small cell variant 1106–7, 1107,
1029smoking 1094squamous cell papilloma
differential diagnosis 855squamous dysplasia/
carcinoma-in-situassociation 908
staging 1094surgery 1105thyroid transcription factor 1
expression 1016, 1018tonofilaments 1103treatment contraindications
1104tumor growth 1103variants 1105–8well-differentiated 1098–9
squamous cell metaplasia 899squamous cell papillomas 850–5alveolar parenchymal
involvement 853–4classification 850clinical features 850clinicopathologic correlation
855cytology 854, 854–5differential diagnosis 855electron microscopy 855etiology 850histopathology 851–4human papilloma virus 850,
852–3, 855immunohistochemistry 855inverted 853, 853–6macroscopic pathology 851malignant transformation 855mixed glandular papilloma
856, 857multiple 851natural history 855papillary squamous cell
carcinoma differentialdiagnosis 1105
pathogenesis 850pathology 853, 854prognosis 855radiographic findings 850–1smoking association 850solitary 851, 851, 852, 852–3squamous cell carcinoma
differential diagnosis1104
squamous dysplasia/carcinoma-in-situ (SD/CIS) 898, 889,894–902
angiogenic 899autofluorescence bronchoscopy
896–7, 908–9basement membrane thickness
898bcl2 protein 904bronchial clearance
compromise 895bronchial epithelium 900CD44v6 906chromosomal aneusomy 907classification 895, 900concurrent squamous cell
carcinoma association 908cytology 899detection 891–2, 896–7diagnosis 898–9, 900, 903
differential diagnosis 900DNA aneuploidy 907environmental irradiation 892etiology 890–2exfoliative cytology 898–9grades of disease 897, 898, 899histologic assessment 900histologic features 895hyperproliferation 903lesion size 895–6macroscopic pathology 895–7microscopic features 897–8mild dysplasia 897, 897, 899,
900–1moderate dysplasia 897, 897,
899neovascularization 898p53 status concordance 904pre-invasive bronchial
lesions 892progression risk 908, 909, 909retinoic acid receptor function
loss 906severe dysplasia 897, 898, 899,
902, 902small cell lung carcinoma
association 909smoking 891, 900squamous metaplasia 891, 892,
894telomerase reverse
transcriptase 906WHO diagnostic criteria 900
squamous epitheliumatypical 901reactive 902
squamous metaplasia 893,893–4, 894
diffuse alveolar damage 348factors associated with 894non-dysplastic 894smoking 893–4squamous dysplasia/
carcinoma-in-situ 891,892, 894
squamous papillary lesions,atypical 901
stannosis 546Stanton hypothesis,
mesothelioma 1467Staphylococcus 152, 176non-coagulase producing 176
Staphylococcus aureus 172abscess 163botryomycosis 164, 176cystic fibrosis 99pneumonia 148, 176
Starling forces, pleural fluid 1409starvation, emphysema 623–4status asthmaticus 565stem cells, lung development 7STK11/LKB1 gene mutation,
lung adenocarcinoma1063
Streptococcab pneumonia 176–7
Streptococcus, hemolytic 164, 165Streptococcus agalactiae
pneumonia 176Streptococcus pneumoniae 147,
153, 164, 177Streptococcus pyogenes 177Streptococcus viridans group
pneumonia 177Strongyloides stercoralis
(strongyloidiasis)316–18, 318
Churg–Strauss syndromedifferential diagnosis 736
clinical features 317diagnosis 317–18epidemiology 316organism 317pathology 317treatment 318
subacute sensory neuropathy,lung carcinoma 973–4
submucosa 15elastosis 54
submucosal glands 23cystic fibrosis 99
subpleural fibrosis 370respiratory bronchiolitis/
RB-ILD 386, 387subpleural lobules 10succinated dehydrogenase
missense mutation,primary pulmonaryglomus tumors 1249
sugar tumor see clear cell tumorof the lung (CCTL)
superficial spreading 1095–6superior vena cava syndrome
970, 1047supernumerary arterial branches
663, 664–5, 666surfactantdeficiency in respiratory
distress syndrome103–4
metabolic dysfunction 106phospholipids 25–6secretion by type II
pneumocytes 25–6synthesis 6
surfactant apoprotein A 1025surfactant protein(s) 4, 26, 1025,
1026surfactant protein A (SP-A) 26,
103–4atypical adenomatous
hyperplasia 925idiopathic pulmonary fibrosis
958immunohistochemistry 1025,
1026lung cancer 958pleomorphic carcinoma 1189variations associated with
respiratory distresssusceptibility 106
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surfactant protein B (SP-B) 26,103–4, 1025
absence 106variations associated with
respiratory distresssusceptibility 106
surfactant protein C (SP-C) 6, 7,26, 103–4
mutations 368variations associated with
respiratory distresssusceptibility 106
surfactant protein D (SP-D)26, 103–4, 428
surfactant therapy, pulmonaryhemorrhage 111
surgical lung biopsy, interstitiallung disease 366
survivin, atypical adenomatoushyperplasia 923
Sweet’s syndrome 833Swyer–James–MacLeod
syndrome 626, 639, 640synaptophysin 1026, 1027, 1164,
1170syndrome of inappropriate
antidiuretic hormonesecretion (SIADH)971, 1153
synovial sarcoma 124, 1281–3biphasic 125, 1516cell of origin 1281classification 1281clinical features 1281clinicopathologic correlation
1283cytology 1283differential diagnosis 1283electron microscopy 1283histopathology 1282–3immunohistochemistry 1283macroscopic pathology 1281–2mast cells 1283mesothelioma differential
diagnosis 1516metastatic 1283molecular findings 1283monophasic 125monophasic spindle cell
tumors 1282–3, 1435natural history 1283pleomorphic carcinoma
differential diagnosis 1193pleural 1517poorly differentiated 1516prognosis 1283radiographic findings 1281
synthetic vitreous fibers 1439,1445, 1462
syphilis 179, 221systemic arterial supply, isolated 85systemic inflammatory response
syndrome (SIRS) 262systemic lupus erythematosus
(SLE) 814–20
acute lupus pneumonitis 815antiphospholipid syndrome
815, 819–20capillaritis 742diffuse alveolar damage 816diffuse alveolar hemorrhage
815–17, 815, 816drug reactions 819interstitial lung disease 817–19lymphocytic interstitial
pneumonia 816nonspecific interstitial
pneumonia pattern 818organizing pneumonia pattern
819pathology 815pleural disease 1425–6pleurisy 1425pleuritis 815pulmonary hemorrhage
syndrome 740pulmonary hypertension 670,
697, 698, 815, 817shrinking lung syndrome 819thromboembolic disease 818vascular disease 815vasculitis 816
systemic sclerosis 820–3autoantibodies 820–1clinical manifestations 820interstitial lung disease 821–2lung cancer 822–3, 958nonspecific interstitial
pneumonia pattern821–2, 821
patchy congestion 698pathology 821pulmonary hypertension 392,
667, 697–8, 822, 822usual interstitial pneumonia
pattern 821–2vascular disease 699
T-cell lymphomas 1343, 1346T-cell prolymphocytic leukemia
1347T-cell rich large B-cell lymphoma
1334T cellsasthma 566Churg–Strauss syndrome 735immune response 154mycobacterial infections 213pulmonary hypertension 675
T helper 2 (Th2) cells 373T helper cells 489, 490Taenia solium (cysticercosis)
333–4clinical features 333diagnosis 334epidemiology 333organism 333pathology 334
tail sign, lung adenocarcinoma1047
Takayasu arteritis 747–9clinical manifestations 747–8diagnosis 747–8differential diagnosis 748epidemiology 747genetics 747giant cell arteritis differential
diagnosis 747, 748histopathology 748laboratory findings 748macroscopic pathology 748natural history 748–9pathogenesis 748prognosis 748–9pulmonary artery involvement
748radiographic findings 748tuberculosis association 748
talc embolism 537talc granulomatosis 537, 600talcosis 536–8, 1417asbestos contamination 536–7,
538pathology 537progressive massive fibrosis
537radiological appearance 537
telomerase reverse transcriptase,human (hTERT) 906, 925
tension pneumothorax 110teratomamediastinal 1286see also pulmonary teratoma
terminal respiratory unit (TRU)910
testicular non-seminomatousgerm cell tumor,metastases 1381, 1399
testicular seminoma, metastases1399
tetralogy of Fallot, pulmonaryhypertension 693–5, 696
TFE3 expression, clear cell tumor1258
TGF-p type II receptor (TpRII) 6thoracic aorta, large vessel arising
from 83thoracic duct trauma 1428thoracic volume, inadequate 91Thorotrast, peritoneal
mesothelioma 1461thrombo-embolism/thrombo-
embolic disease 682antiphospholipid syndrome 820chronic recurrent 768genetic factors 679–80lung infarct 685post-thrombotic remnants 683pulmonary artery occlusion
680pulmonary hypertension
666–7systemic lupus erythematosus
818thrombosis 112, 680
thrombotic arteriopathy 679–86,687
associated conditions 679congestive vasculopathy 683–4differential diagnosis 684–6epidemiology 679–80fibrotic remnants 682–3histopathology 680–3pulmonary infarcts 683–4risk factors 679–80small vessel remodeling 683thrombus organization 680–2vascular lesions 681
thrombusepithelioid granulomas 682organization 680–2
thymic tumors 1510–2thymomaintra-pulmonary 1283–5mediastinal 1285pleural 1511, 1512
thyroid carcinomametastases 1395thyroid transcription factor 1
expression 1019see also papillary thyroid
carcinomathyroid transcription factor 1
(TTF1) 910, 1015clones 1024cytoplasmic staining 1023embryology role 1015expression 1015, 1016carcinoid tumor 1018, 1019,1165
extra-pulmonaryneuroendocrine tumors1022
extra-pulmonary small cellcarcinoma 1020, 1022
large cell carcinoma 1016,1019
lung adenocarcinoma 1016,1017
lung tumors 1016non-pulmonary tumors1019, 1021
sarcomatoid carcinoma1018, 1020
small cell lung carcinoma1016, 1018
small cell lung carcinomaand Merkel cellcarcinoma of skincomparison 1022
squamous cell carcinoma1016, 1018
lung adenocarcinoma 1061,1066
lung cancer prognosis 1020mesothelioma and lung
adenocarcinomadistinction 1495–6
monoclonal antibodycomparison 1021
Index
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thyroid transcription factor 1(TTF1) (cont.)mutations 1016neuroendocrine tumors 1165NKX2–1 amplification 1064nuclear staining 1023pleomorphic carcinoma 1189squamous cell carcinoma
immunohistochemistry1103
structure 1015tin exposure 546titanium, pleural plaques 1439titanium pneumoconiosis
545–6, 548TNM classification 48fixed tissue/fresh tissue 48pleural invasion 48
Toll-like receptor(s) (TLRs)153, 229–30
Toll-like receptor 7 (TLR-7) 28Toll-like receptor 9 (TLR-9) 28tongue carcinoma, metastases
1388tonofilaments, squamous cell
carcinoma 1103Toxocara (toxocariasis) 317, 319,
319–20, 736clinical features 319diagnosis 320epidemiology 319organism 319pathology 319–20, 320
Toxoplasma gondii(toxoplasmosis) 301–4
clinical findings 301–2congenital 301–2diagnosis 302–3differential diagnosis 303epidemiology 301hosts 301human infection 301immunohistochemistry 303interstitial pneumonitis 302life cycle 301necrotizing pneumonia 302organism 301pathology 302, 303radiographic appearance
302, 302reactivation of latent infection
302treatment 303–4
trabeculae 10tracheaanatomy 7–8congenital malformations
66–71development 1, 4, 6fibrous webs 71growth 6length abnormalities 66mucus retention cysts 71organization 7–8
tracheal agenesis 66–7, 67
classification 67diagnosis 67embryology 67malformation patterns 67presentation 67
tracheal stenosis 67–9, 71age 69associated abnormalities 69classification 67diffuse 68, 68extrinsic 69funnel-shaped 68–9intrinsic 68–9mortality 69segmental 69symptom severity 69vascular anomalies 69
tracheoesophageal fistula 70–1, 71associated malformations 70etiology 70outcomes 71subtypes 70–1
tracheobronchial cartilage 53–4tracheobronchial papillomatosis
854tracheobronchial sicca 824–5tracheobronchomegaly 71, 430tracheobronchitis, viral infections
182, 184, 185–6tracheobronchopathia
osteochondroplastica635–6, 636
tracheobronchopathiaosteoplastica 71
tracheomalacia 69–70, 70traffic-related pollution 952transbronchial lung biopsy (TBBx)
59–60, 769–70, 774efficacy 60, 60–1high utility 60–1probably/possibly diagnostic 61reliability 60, 60–1unreliable uses 61
transcription factors 5, 906transforming growth factor b
(TGF-b) 428, 429, 1467transforming growth factor b
(TGF-b) receptor 2mutations 428
transforming growth factor b1(TGF-b1) 6
transfusion-related acute lunginjury (TRALI) 595–6
transplant-associatedvasculopathy (TAV)792–3
trastuzumab toxicity 593TREM-1 153–4, 1412trematodes 322–8food-borne 328
tremolite, environmental pollution1437–8, 1459–60
Treponema pallidum 174, 179triazole, Aspergillus infection
238–9
Trichomonas 307Trichophyton rubrum 228Trichosporon, Japanese summer-
type hypersensitivitypneumonitis 459
triggering receptor expressedon myeloid cells-1(TREM-1) 153–4, 1412
trisomy 21, development-relatedairspace enlargement 623
Tropheryma whipplei (Whippledisease) 174, 179, 413
tropical pulmonary eosinophiliasyndrome 308–11, 311
clinical features 309diagnosis 310–11epidemiology 308organism 308–9pathogenesis 311pathology 309–10
Trypanosoma brucei (Africantrypanosomiasis) 295,296, 297
Trypanosoma cruzi (Chagasdisease) 290–1, 295–7,296
clinical features 295diagnosis 295differential diagnosis 295–7epidemiology 295organism 295pathology 295transmission 295vector 295
TSC gene mutations 859, 926,1249–50, 1254
tuberculin skin test 209tuberculoma 216, 217tuberculosis see Mycobacterium
tuberculosis(tuberculosis)
tuberculous bronchopneumonia217, 217
tuberculous empyema 1424tuberous sclerosis complexangiomyolipoma 1249, 1250clinical features 857–8genetics 857, 926lymphangioleiomyomatosis
1249–50, 1252micronodular pneumocyte
hyperplasia 917multifocal micronodular
pneumocytehyperplasia 857
tuft cells see brush cellstularemia 178tumor emboli 1389–90differential diagnosis 1390histopathology 1389–90location 1389macroscopic pathology 1389non-thrombotic 688pulmonary embolism 1389radiographic findings 1389
tumor suppressor genesmesothelioma 1466, 1467pulmonary preinvasive disease
903–4, 906tumorlets 21, 1172–3, 1176–7,
1177, 1229tumour necrosis factor a (TNFa)
213tungsten carbide
pneumoconiosis 541–3tyrosine kinase inhibitorsresistance 1062toxicity 592, 593
tyrosine kinase signalingpathway 905, 923–5
ulcerative colitis 833–5ultrastructure of lungs 13–17upper respiratory system 7upstream regulatory factors
(USF) 906uranium miners, lung cancer
891, 953urinothorax, pleural effusion
1411urothelial carcinoma, metastases
1383, 1393usual interstitial pneumonia (UIP)
114, 367, 368–74, 524abnormal tissue repair 373–4apical cap differential
diagnosis 1423apoptosis abnormalities 374asbestosis differential
diagnosis 519, 521–2associated conditions 369bronchoalveolar lavage 369chronic eosinophilic
pneumonia 572, 573clinical presentation 368–9connective tissue disease
371, 804cytokine polymorphisms 374dermatomyositis 826desquamative interstitial
pneumonia differentialdiagnosis 389
differential diagnosis 370–2discordance in diagnosis 371drug-induced lung disease
587–8etiology 368fibroblastic foci 375fibrotic interstitial pneumonia
384Hermansky–Pudlak syndrome
differential diagnosis 421histologic features 372hypersensitivity pneumonitis
455, 457, 460–3differential diagnosis 445
immune system 373lymphangioleiomyomatosis
differential diagnosis1255
Index
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lymphoid proliferation 1318natural history 374neutrophils 373pathogenesis 372–4polymyositis 826prognosis 374radiological findings 369rheumatoid arthritis 809scleroderma 821–2Sjögren syndrome 824superimposed histological
patterns of lung disease371
see also idiopathic pulmonaryfibrosis (IPF)
uterine carcinoma, metastases1384, 1398
uterine leiomyoma 1247, 1398uterine leiomyosarcoma,
metastases 1398uterine tumors, metastatic
878–9
vaccinationmeasles 193viral infections 183
VACTERL (Vertebral anomaly,Atrial atresia, Cardiac,Tracheo-Esophagealfistula with atresia,Renal anomalies andLimb abnormality)spectrum 67
bronchomalacia 72–3horseshoe lung 75lung agenesis 75tracheoesophageal fistula 70
vacuum chamber formalinfixation, wedgebiopsy 45
Varicella pneumonia 183, 199,200
varicella zoster virus (VZV)197–8
vascular cell adhesion molecule 1(VCAM-1) 680
vascular endothelial growthfactor (VEGF) 5, 109,620, 864, 905–6
vascular endothelial growthfactor 1 (VEGF-1) 677
ANCA-associated diseases711–40
autoimmune disease 700Behçet’s syndrome 749–52capillaritis 740–5categorization 712Churg–Strauss syndrome
734, 736classification 711definition 711diagnosis 700drug-induced lung disease
589giant cell arteritis 745–7
necrotizing sarcoidgranulomatosis 495
polyarteritis nodosa 700, 743–5pulmonary hemorrhage
syndromes 740–5pulmonary hypertension 700rheumatoid arthritis 814systemic lupus erythematosus
816Wegener’s granulomatosis 720
vasculogenesis 4, 5veno-occlusive disease 589venous thromboembolism
679–80, 975ventilationcomplications 111see also mechanical ventilation
ventilation/perfusion mismatch,meconium aspiratesyndrome 112–13
vermiculite 539–40video-assisted thoracoscopic
surgery (VATS) 43,49, 977
biopsy 59–60, 770vimentin, sarcomatoid
mesothelioma 1502viral infections 116–18bacterial superinfections 185,
189–90bronchiolitis 185–6cellular changes 187diffuse alveolar damage 184,
186–7epidemiology 182–4fungal superinfections 185hematogenous dissemination
184host factors 183human 182injury patterns 186lung carcinoma 953–6lung injury pattern 185lung transplantation 770, 783–5pathology 182–202pathophysiology 184patterns of disease 182pneumonia 147predisposing factors 182pulmonary defenses 184–5radiographic appearance 184seasonality 184tracheobronchitis 182, 184,
185–6transmission 183–4vaccination 183see also named viruses and
diseasesvisceral larva migrans 308, 316,
318–20vitamin A deficiency 894, 958–9vitamin C 959–60vitamin D 959–60vitamin E 959–60volatile inhalant abuse 600
volume doubling time (VDT),lung carcinoma 968
von Hippel–Lindau disease 861von Recklinghausen’s disease
1239voriconazole 239, 243, 244
Waldenström’smacroglobulinemia 1331
Warthin–Finkeldey cell 193wedge biopsyfixation 44–5formalin fixation 45frozen section 44indications 43multiple lobe sampling 44nodular density 44open 43–4processing 43–4, 45
Wegener’s granulomatosis713–29
A1AT deficiency association714
active disease 728acute eosinophilic pneumonia
differential diagnosis 580acute interstitial pneumonia
differential diagnosis 382age effects 714airspace disease 717airway lesions 727airway necrotizing lesions 715airway wall thickening 717alveolar hemorrhage 727ANCA 729, 834–5antigens 712, 728subtypes 714testing 713, 728
autoantibodies 711, 728bronchiolitis 718capillaritis 742Churg–Strauss syndrome
differential diagnosis734, 735
clinical manifestations 714,714–15
collagen necrosis 720cytology 728differential diagnosis 728–9epidemiology 713–14filarial disease differential
diagnosis 310–11fulminant 727genetics 714giant cell arteritis differential
diagnosis 747Goodpasture’s syndrome
overlap 739–40granulomatous bronchiolitis
645–6granulomatous inflammation
724–5, 726–7granulomatous necrosis 724,
725hemorrhage 718, 727
histopathology 718–28historical aspects 713imaging techniques 715incidence 713–14infections 715, 728inflammation 728inflammatory bowel disease
differential diagnosis834–5
laboratory findings 728linear densities 717lymphadenopathy 717lymphomatoid granulomatosis
differential diagnosis1334
macroscopic pathology718, 719
malignancy risk 715mediastinal masses 717microabscesses 723–4, 723,
724microscopic polyangiitis
differential diagnosis731
natural history 729necrotizing sarcoid
granulomatosisdifferential diagnosis 498
neutrophils 728nodules 715–17, 718, 718organ involvement 720palisading granuloma
725, 726palisading histiocytes 725–6pathogenesis 728, 729pleural disease 1424, 1424–5,
1425polyarteritis nodosa
differential diagnosis744–5
prognosis 729pulmonary endometriosis
differential diagnosis 879pyoderma gangrenosum
differential diagnosis832–3
radiographic findings 715–18,716, 717
splenic 719superficial protracted phase
715tissue necrosis 720, 723, 724treatment 727, 729tuberculosis differential
diagnosis 221tumorous masses 727upper respiratory tract
involvement 714, 720vasculitis 720, 722, 723
weight loss, COPD 622–3welder pneumoconiosis 547–9aluminum fumes 548–9lung cancer association 549pathology 548, 548, 549radiographic appearance 548
Index
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well-differentiated fetaladenocarcinoma(WDFA) 878–9
Werner’s syndrome 960Westermark sign 666–7, 667Whipple disease 174, 179, 413Wilms’ tumor 1376–7, 1389
Wilms’ tumor gene product(WT1) 1497–8, 1503
Wilson–Mikity syndrome 109wood smoke exposure 553Wucheria bancrofti 308–9dirofilariasis differential
diagnosis 313
eosinophilic pneumonia 310life cycle 310microfilaria 310
xenobiotic metabolizing enzymes(XMEs) 891, 907, 926,929
xenobiotics 950xerotrachea 824–5
Yersinia pestis 175, 179
zebra bodies 418, 422, 426zeolites 538–9, 1437
Index
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