j0305257 Systemic pathology The respiratory tract j0305257 Histology of respiratory tract 02_06 j0305257 Cellular components of bronchial mucosa 02_07 j0305257 The respiratory membrane respmemb j0305257 Chronic polypous rhinitis û chronic proliferative inflammation û û etiology: ð chronic irritation ð ð allergy ð ð repeated acute inflammations j0305257 Chronic polypous rhinitis û Gross: ð mucosal polyps, often multiple ð variable size (mm – 2 cm) ð û Micro: ð oedematous mucosal connective tissue ð lymphoplasmocytic reactive infiltration, admixture of eosinophils, +/- neutrophils ð mucinous hyperplasia ð covered by hyperplastic respiratory epithelium, squamous metaplasia possible j0305257 Polypous chronic rhinitis 1 Epithelium with squamous metaplasia 2 Thickened basal membrane 3 Oedematous stroma with eosinophilic and plasma cell infiltration, dilated lymphatic vessels 1 2 3 j0305257 Polypous chronic rhinitis 1 Ciliated epithelium 2 Oedematous stroma with inflammatory infiltrate 1 2 j0305257 Polypous chronic rhinitis polyp4002 1 Congested capillary 2 Eosinophils 3 Oedematous stroma 1 2 3 j0305257 Laryngeal carcinoma ûSequence: in squamous epithelium: hyperplasia – atypical hyperplasia – intraepithelial neoplasia (dysplasia – carcinoma in situ) – invasive carcinoma. û In respiratory epithelium: squamous metaplasia - intraepithelial neoplasia (dysplasia – carcinoma in situ) – invasive carcinoma. û Commonly multiple dysplastic foci and/or sequential carcinomas in upper respiratory/GIT – same oncogenic factors, field theory û j0305257 Laryngeal carcinoma ûRisk factors: smoking, alcohol, HPV, (asbestos, irradiation) ûPapilloma: HPV, solitary (adults) x multiple (papillomatosis in children). Benign, possible recurrence ûCarcinoma: mainly squamous cell ca, rare adenocarcinoma ûOn vocal cords, supravocal, infravocal ûClinical features: hoarseness, later pain, dysphagia, bleeding û û j0305257 Pseudomembranous tracheitis ûDiphteria, influenza, scarlet fever, mumps, etc. ûIatrogenic – intubation; uremia. û ûRisk of ulceration – chondromalatia – cartilage breakdown – perforation - mediastinitis û û j0305257 Pulmonary infarction û aetiology: ð thrombembolism of a. pulmonalis branches in the setting of compromised cardiovascular status (passive venous congestion) û typically hemorrhagic ð û often in lower lung lobes adjacent to pleura û û often multiple û û healing: ð granulation tissue, later formation of fibrous scar ð j0305257 Pulmonary infarction û aetiology: ð thrombembolism of a. pulmonalis branches in the setting of compromised cardiovascular status (passive venous congestion) ðuncommonly local thrombosis/arterial closure (in carcinoma) û typically hemorrhagic ð û often in lower lung lobes adjacent to pleura û û often multiple û û healing: ð granulation tissue, later formation of fibrous scar ð j0305257 Hemorrhagic pulmonary infarction û Gross: ð wedge-shaped sharply demarcated focus ð dark red-blue (new), yellowish-grey (older) ð variable size ð firmer consistency ð û Micro: ð coagulative necrosis of lung parenchyma ð large extravasations of erythrocytes ð formation of abscess by secondary infection ðreactive acute fibrinous pleuritis ðhealing – scarring + emphysema (diff.dg. x tumor) ð ð j0305257 Hemorrhagic pulmonary infarction infarkt plic 20x 01 1.Necrotic focus 2.Lung parenchyma 1 2 j0305257 Hemorrhagic pulmonary infarction infarkt plic 100x 01 Necrotic lung parenchyma j0305257 Alveolar oedema û fluid accumulation in alveoli û û clinically: ð expectoration of bubbly watery pinkish sputum ð û pathogenesis: ð ↑ vascular permeability (injury to the alveolar-capillary wall) ð ↑ vascular hydrostatic pressure ð ↓ intravascular osmotic pressure ð lymphatic drainage obstruction û j0305257 Alveolar oedema û Complications: ↑ risk of infection û Gross: ð lungs enlarged, heavy, congested ð bubbly fluid flowing out of the tissue +/- present in bronchi ð û Micro: ð alveoli filled with pink, homogenous fluid + air bubbles ð dilatation and hyperemia of alveolar wall capillaries ð û j0305257 Alveolar oedema edem plic 100x 1. Oedematic fluid 2. Dilated septa 3. Dilated capillary 1 2 3 j0305257 Amniotic fluid aspiration û minor aspiration usual during birth ð clinically insignificant ð û massive aspiration associated with fetus asphyxia ð umbilical cord or placental disorders ð û clinic: ð changes in fetal heart rate – immediate medical intervention necessary! j0305257 Amniotic fluid aspiration û Micro: ð keratin masses in bronchi and alveoli ð amniotic cells ð lanugo (thin primary hairs) ð meconium bodies (from fetus intestinal content) ð infected amniotic fluid → fetal death, adnate pneumonia û j0305257 Amniotic fluid aspiration, keratin in bronchiole 12x200 1 Masses of keratin 2 Bronchial epithelium 3 Multinuclear cell 1 2 3 j0305257 Amniotic fluid aspiration, keratin in alveoli 12x400x2 1 Masses of keratin 2 Meconium 3 Alveolar wall 1 2 3 j0305257 Chronic pulmonary venous congestion û associated with chronic left-sided cardiac insufficiency ð etiology: • ischemic heart disease, systemic hypertension, valvular disorders, cardiomyopathy • û clinically („asthma cardiale“): ð cough • rusty sputum ð shortness of breath (dyspnoea) • ortopnoea • paroxysmal nocturnal dyspnoea – relieved by sleeping with elevated head („additional pillows needed“) û û j0305257 Chronic pulmonary venous congestion û Gross: ð slightly enlarged lungs ð solid consistency ð rusty-brown color • rusty/cyanotic lung induration • û Micro: ð congestion of alveolar capillaries ð alveolar hemorrhage with siderophages: • histiocytes with cytoplasmic granules of hemosiderin ð fibrotization of alveolar walls j0305257 Chronic pulmonary venous congestion chron venostáza plíce 1. Oedematic fluid 2. Enlarged hyperemic septa 3. Siderophages 1 2 3 j0305257 Chronic pulmonary venous congestion chron venostáza plíce- detail 1. Oedematic fluid 2. Enlarged hyperemic septa 3. Siderophages 1 2 3 j0305257 Chronic pulmonary venous congestion Perls‘ reaction – iron pigment hemosiderin colored blue j0305257 Chronic pulmonary diseases û Obstructive – airway d.-↑in resistance to airflow due to partial/complete obstruction at any level (trachea – bronchi – bronchioles) ðchronic bronchitis ðbronchiectasis ðasthma ðbronchiolitis ðemphysema û û Restrictive – reduced expansion +/- decreased total lung capacity. ð chronic interstitial and infiltrative disorders ðchest wall disorders j0305257 Chronic obstructive pulmonary diasease û Clinical syndrome – productive cough, dyspnoea, end-stage – respiratory failure û Pathology: chronic bronchitis +/- emphysema û Major trigger – cigarette smoking, air pollution û Complications: recurrent bacterial/viral infections, cor pulmonale, pneumothorax, lung cancer, may progress to respirátory failure û j0305257 Chronic bronchitis û part of spectrum of ch. obstructive pulmonary disease, duration at least 3 months in 2 years û Simple ch. b. ð productive cough, no airflow obstruction û Chronic asthmatic bronchitis ð intermittent bronchospasm, hyperreactive bronchi û Obstructive ch. b. ð chronic obstruction, usually + emphysema û j0305257 Asthma bronchiale ûchronic inflammatory disease of bronchial tree, recurrent attacks of bronchospasm with exspiratory dyspnoea, cough, mucus hypersecretion ûincreased irritability of the bronchial tree with paroxysmal narrowing of the airways. û status asthmaticus: ð increased frequency of attacks – permanent bronchospasm ð may be lethal û variants: ð atopic (extrinsic): •environmental factors, type I hypersensitivity reaction, IgE, mast cells degranulation, increased vascular permeability and mucus secretion + eosinophils activation •bronchioloconstriction, distal collapse or overinflation ð non - atopic (intrinsic): • triggered by infection (viral), subsequent hyperreactive state of vagal receptors, reaction after nonspecific irritation ð drug-induced: i.e. aspirin, NSAID, cytokine dysbalance, commonly + urticaria, rhinitis ð occupational: variable etiology (type I+III hypersensitivity) and stimulating agents û j0305257 Asthma bronchiale û Gross: ð acute changes: bronchospasm + emphysema/collapse, mucus plugs in peripheral bronchi and bronchioles, bronchial inflammatory infiltrate ð chronic airway remodeling: hypertrophy/hyperplasia of smooth muscle and mucous glands ð û Micro: ð intraluminal: • mucus (Curschmann spirals), eosinophils, Charcot-Leyden crystals, cellular detritus • ð bronchial wall: • oedema of the mucous membrane • thickening (collagenisation) of the sub-basement membrane tissue • mucous glands hypertrophy, eosinophil-rich inflammatory infiltrate, ↑ vascularity, MALT ð j0305257 Asthma bronchiale asma copy j0305257 Image008 Asthma bronchiale j0305257 Bronchiectasis û permanent abnormal dilatation of bronchi û arising from the weakening of the walls or changes in air pressure û morphology: ð cylindrical ð saccular ð fusiform j0305257 Bronchiectasis û aetiology: ð congenital/hereditary conditions: • cystic fibrosis • Kartagener syndrome (structural abnormalities of the cilia, leading to persistent infections) • – ð acquired: • chronic inflammations • Postinfectious ( incl. necrotizing pneumonia) • Bronchial obstruction (tumor, foreign bodies, mucus) • Other (SLE, rheumatoid arthritis, etc.) • radiotherapy • changes of the pressure – chronic pulmonary collapse – j0305257 Bronchiectasis û complications: ð inflammations: • chronic purulent bronchitis • bronchopneumonia including abscess formation • secondary infection incl. fungal (aspergilloma) • metastatic infection (brain abscess) • ð emphysema ð fibrosis, pulmonary hypertension and cor pulmonale ð ð secondary AA amyloidosis j0305257 Bronchiectasis image00110 BRONCHIECTASIA kopie j0305257 Bronchiectasis Image011 j0305257 Pulmonary emphysema û regressive change û û abnormal permanent enlargement of the airspaces + alveolar wall destruction in the pulmonary tissue û û aetiology (combination of several factors): ð smoking ð deficiency of α1-antitrypsin ð other û û types: ð alveolar: • acute • chronic ð ð interstitial – airway rupture (trauma) û j0305257 Alveolar emphysema û acute: ð alveolar septa are not destroyed ð rather pulmonary hyperinflation or distention ð û chronic: ð permanent enlargement of airspaces distal to terminal bronchioles ð destruction of alveolar walls ð part of COPD (chronic obstructive pulmonary disease) • combination of chronic bronchitis and chronic emphysema ð j0305257 Emphysema û pathogenesis and complications: protease-antiprotease + oxidant-antioxidant imbalance in the setting of inflammatory response, bronchiolitis, later possible maladaptive immune response ðthinning of alveolar walls and capillaries → ðreduced blood supply → ðcomplete destruction of alveolar walls → ðdifficult expiration + decreasing of lung capacity → ðhypoxemia → endothelial cell dysfunction ðmedial hypertrophy, intimal fibrosis + vasoconstriction → ðsecondary pulmonary hypertension → → ðcor pulmonale ð j0305257 Alveolar emphysema û types: ð centrilobular (centriacinar): • upper lobes – apex, more in males, • most commonly seen in smokers without congenital a1-antitrypsin deficiency (but + chronic bronchitis), possible professional disease - dust • ð panacinar: • often lower lung zones; significant microscopic changes; a1-antitrypsin deficiency, old age • ð distal acinar (paraseptal): • adjacent to pleura, upper lobes foci of fibrosis, formation of cystlike structures – bullae (pneumothorax risk) • ð irregular: • associated with scarring, usually postinflammatory j0305257 Alveolar emphysema û Gross: ð enlarged, voluminous lungs, light, pale, dry, emphysematous bullae ð û Micro: ð thinning and destruction of alveolar walls ð ð deformation of bronchiolar walls ð ð chronic inflammatory changes j0305257 Emphysema Image013 j0305257 Normal lung and pulmonary emphysema j0305257 Bullous emphysema j0305257 Panacinar emphysema 1 Enlargement of airspaces with thinning and destruction of alveolar septa 2 Bronchiole with mucous secretions 1 2 1 2 j0305257 Pulmonary inflammations - classification ûEtiology û Infections û Non-infectious, commonly from the group of chronic interstitial lung disease (hypersensitivity pneumonitis, nonspecific interstitial pneumonia, etc.) û û j0305257 Pulmonary inflammations - classification û superficial: ð lobar pneumonia ð bronchopneumonia ð û interstitial ð purulent (abscess, gangrene) ð non-purulent • infectious (acute) – atypical pneumonia • non-infectious (chronic) j0305257 Pneumonias û Community acquired acute pneumonia ð Str. pneumoniae ð Haemophilus influenzae ð Staph. aureus ð Legionella pneumophila ð Klebsiella pneumoniae ð Pseudomonas ð others (Moraxella, …) ð j0305257 Pneumonias û Community acquired atypical pneumonia ð Mycoplasma pneumoniae ð Chlamydia ssp. ð Coxiella burnetii (Q-fever) ð viruses – SARS-CoV-2, influenza, parainfluenza, adenovirus, RS virus, etc. ð j0305257 Pneumonias û Hospital acquired pneumonias ðG- rods, Enterobacteriaceae (Klebsiella, E.coli, Pseudomonas) ð Staph. aureus (methicillin resistant) ð û Aspiration pneumonia ð anaerobic oral flora + aerobic bacteria (incl. Str., Staph., Haemophilus etc.) j0305257 Pneumonias û Chronic pneumonia ð Nocardia ð Actinomyces ð Granulomatous: mycobacteria (TBC, atypical), Histoplasma, other fungi û Necrotizing pneumonia and lung abscess ð Anaerobic bacteria (+/- mixed aerobic infection) ð Staph. aureus, Klebsiella, Str. pyogenes ð some anthropozoonozes (plague, anthrax) ð j0305257 Pneumonias û P. in the immunocompromised host ð CMV ð Pneumocystis jirovecii ð Mycobacterium avium-intracellulare ð Invasive aspergillosis ð Invasive candidiasis ð „usual“ infections j0305257 Lobar pneumonia û superficial diffuse fibrinous inflammation û affecting major part / entire lobe of a lung ð similar histological features in the same time ð older/immunocompromised patients → lethal without antibiotic therapy û untreated – 4 stages: ð congestion (+ oedema) ð red hepatization (inflammatory infiltrate + congestion) ð grey hepatization (fibrin) ð resolution (resorption) j0305257 Lobar pneumonia û healing: ð ad integrum ð complications: • empyema • abscess • carnification • sepsis • metastatic purulent inflammation – e.g.leptomeningitis, pericarditis, endocarditis… û j0305257 Lobar pneumonia, red hepatization j0305257 Lobar pneumonia, grey hepatization j0305257 Lobar pneumonia plíce 40x 1. Alveolar walls 2. Alveoli filled with fibrinous exsudate 1 2 2 j0305257 Lobar pneumonia HE 40x 1. Alveolar walls 2. Alveoli fulfilled with fibrinous exsudate 1 2 2 j0305257 Lobar pneumonia HE 100x 1. Alveolar walls 2. Fibrinous exsudate with fibroblasts 1 2 2 j0305257 Bronchopneumonia û superficial type of pneumonia characterized by multiple foci of isolated, acute consolidation, affecting one or more pulmonary lobules û û inflammation spreads from bronchi û û aetiology: ð streptococcus, staphylococcus, haemophilus, klebsiella ð legionella – micro: • fibrinous purulent bronchopneumonia associated with fibrinous pleuritis û possible secondary confluent inflammation, overlap patterns û inflammatory complications: ð pleuritis ð abscess ð sepsis j0305257 Bronchopneumonia û Commonly secondary – prior viral pneumonia, ð in chronic lung diseases, debilitating diseases, immunologic defect, aspiration, coma … ð various stages of inflammation in the same time û Gross: ð oedema, hyperemic tissue with small grey-yellow foci û Micro: ðtypes of exsudate: • serous • suppurative (purulent) +/- fibrinous ð abscessing form – suppurative destruction of alveolar walls û j0305257 Bronchopneumonia brpn1 brpn2 copy j0305257 Abscessing bronchopneumonia plíce povrch abscesy plíce řez abscesy j0305257 Purulent bronchopneumonia BP 200x 1. Alveolar walls 2. Alveoli filled with neutrophils 1 2 j0305257 Abscessing bronchopneumonia BP 100x 1. Alveolar walls 2. Abscess with destruction of alveolar walls 1 2 2 j0305257 Infectious interstitial pneumonia û Etiology: ð viruses (incl. in COVID-19, rubeola, varicella) ð mycoplasma, chlamydia, coxiella, etc. ð pneumocystis û Symptoms: ðfever, dyspnoea, dry cough, auscultation may be normal (empty alveoli), x massive changes on X-ray û Healing: ð ad integrum ðprogression incl. ARDS ð secondary bacterial pneumonia ð cryptogenic organizing pneumonia possible j0305257 Infectious interstitial pneumonia û Gross: focal / confluent, red-blue, congested, usually no pleuritis û Micro: ð 1) common histological features: • oedema and dilatation of alveolar walls • interstitium with mononuclear infiltrate (lymphocytes, macrophages, plasma cells) • possible ARDS - „hyaline membranes“ formation – necrotic pneumocytes and fibrin – eosinophilic material lining the lumen of alveoli j0305257 Infectious interstitial pneumonia ð 2) inclusion pneumonia: • typical inclusions and cytopatologic changes of pneumocytes • CMV: – large pneumocytes with basophilic intranuclear inclusions • Varicella, adenovirus: – intranuclear inclusions • Measles: – giant cell pneumonia – multinucleated cells in alveoli and bronchioli (Warthin-Finkeldey cells) • Pneumocystis pneumonia û j0305257 Covid -19 in the lungs ûGeneral appearance of interstitial viral pneumonia ûPathogenesis ðCythopatic viral effect on mucosa + cillia damage ðSurface S protein binding on ACE2 receptor ûVasculopathy of the alveolocapillary membrane, microangiopathy + thrombosis ûComplications: ARDS, septic shock, secondary bacterial superinfection j0305257 COVID-19 lung pathology ûInterstitial pneumonia w. lymphocytic infiltration ûintracellular viral particles incl. in pneumocytes ûGiant/hyperplastic pneumocytes ûDiffuse alveolar damage – DAD/ARDS û ûVascular changes incl. stasis of inflammatory cells, fibrinoid necrosis, microthrombi, deposition of intraalveolar fibrin û j0305257 COVID-19 lung pathology PMC full text:Int J Legal Med. 2020; 134(4): 1285–1290. Published online 2020 Jun 5. doi: 10.1007/s00414-020-02319-8 DAD, oedema, haemorrhage, fibrin deposition, TTF-1+ atypical pneumocytes j0305257 Covid -19 in the lungs ûHistopathological findings in COVID-19 lungs: the virus-induced lung injury with temporal heterogeneity: A - alveolar hyaline membrane (green arrow); B - alveolar-capillary barrier injury with hemorrhage (green arrows); C - acute fibrinous organizing pneumonia (dark blue circle) and organizing pneumonia (dark green circle); and D - pulmonary intravascular thrombotic events. copy j0305257 COVID-19 Cell virus-induced changes ûMultinucleated enlarged pneumocytes (or other cells incl. endothelial - syncytia) with large nuclei, prominent nucleoli in alveolar spaces and other tissues ûIntranuclear inclusions û j0305257 Acute capillaritis/alveolitis j0305257 DAD – 14th day j0305257 Chronic DAD – lung fibrosis j0305257 CMV pneumonia j0305257 Pneumocystis pneumonia û etiology: ð Pneumocystis jirovecii •(opportunistic fungal infection, immunocompromised patients) ð û Micro: ð widened alveolar septa, intraalveolar bubbly eosinophilic material: • pneumocystis capsules ð special histological stains: • Groccott silver impregnation (black) • Giemsa (blue) • PAS j0305257 Pneumocystis pneumonia HE 100x 1. Alveolar walls filled with monocellular infiltration 2. Bubbly eosinophilic material 1 2 j0305257 Pneumocystis pneumonia HE400x 1 2 1. Alveolar walls filled with monocellular infiltration 2. Bubbly eosinophilic material j0305257 Interstitial lung diseases û Form: ðacute alveolar damage (ARDS, radiation pneumonitis, diffuse intrapulmonary haemorrhage – Goodpasture‘ sy) ðchronic interstitial lung disease • Fibrosing –Idiopathic pulmonary fibrosis (Usual interstitial pneumonia) –Nonspecific interstitial pneumonia –Cryptogenic organizing pneumonia –Associated w. connective tissue diseases (rheumatoid arthritis) –Drug reaction –Pneumoconioses • Granulomatous (sarcoidosis, hypersensitivity pneumonitis - extrinsic allergic alveolitis) • Eosinophilic • Smoking related (desquamative interstitial pneumonia etc.) • Other j0305257 Diffuse alveolar damage (Acute Respiratory Distress Syndrome) û DAD (ARDS, RDS) û clinical: ð progressive respiratory insufficiency associated with shortness of breath and hypoxia, high mortality ð û Etiology: ð Primary ARDS: • lung inflammation/infection, aspiration of gastric content, mechanical trauma incl. chest contusion, fat embolism, near-drowning, ionizing radiation, inhaled irritants (smoke, chemicals), ð Secondary ARDS: • trauma (head) or sepsis • acute pancreatitis • renal insufficiency (uremia) • burns • hematologic conditions – DIC, multiple transfusions •chemical injury (heroin overdose, acetylsalicylates, …) • • j0305257 Diffuse alveolar damage (Acute Respiratory Distress Syndrome) û Gross: ð heavy lung ð dark red color ð boggy ð û Micro: ð exsudative phase: • capillary congestion, oedema, hyaline membranes formation within 48 hours • ð proliferative phase: • epithelium regeneration (type II. pneumocytes) • hyaline membranes ingested by macrophages • proliferation of fibroblasts in alveolar walls -> pulmonary fibrosis possible û j0305257 Diffuse alveolar damage (Acute Respiratory Distress Syndrome) ARDS 1. Hyaline membranes 2. Hyperemic septa 1 1 2 j0305257 Diffuse alveolar damage (Acute Respiratory Distress Syndrome) ARDS-detail 1 2 1. Hyaline membranes 2. Hyperemic septa j0305257 CMV pneumonia - ARDS j0305257 6.3 DAD, proliferative phase - fibrotic stage – distinctly thickened interalveolar septa with a chronic inflammatory infiltrate. Obrázek2 j0305257 Idiopathic pulmonary fibrosis ûClinical-radiologic-pathologic diagnosis û synonymic – cryptogenic fibrosing alveolitis û histologic pattern of „usual interstitial pneumonia“ (UIP): û Etiology: abnormal epithelial repair – myo/fibroblastic proliferation • intrinsic problem + exogenous factor (? occupational, smoking) û Dismal prognosis: progressive dyspnoea, hypoxemia, lung failure in cca 3 yrs, therapy - lung transplantation only û û j0305257 Idiopathic pulmonary fibrosis û û usual interstitial pneumonia“ (UIP): ð70% of all of idiopathic interstitial pneumonias ð etiology: • in some connective tissue diseases or in association with abnormalities of serum proteins • smoking, asbestosis • unclear ð ðMicro: •subpleural and a paraseptal foci of fibroblasts/fibrosis and chronic inflammatory infiltrate, cystic spaces - honeycombing • irregular distribution of histological features – temporal heterogeneity • j0305257 Idiopathic pulmonary fibrosis û non-specific interstitial pneumonia (NSIP): ðdifferent histologic/clinical pattern ðcommonly women, without smoking association ð ð better prognosis • treated with corticosteroids • ð Micro: • chronic interstitial inflammation +/- fibrosis • no honeycombing • regular distribution of changes • û j0305257 Usual interstitial pneumonia 15x20 1 Fibrosis 2 Compressed alveoli 1 1 2 2 j0305257 Usual interstitial pneumonia 15x100 1 Thickened septa 2 Vessels 3 Hyperplastic epithelium 4 Neutrophils in alveoli 1 2 3 4 j0305257 Usual interstitial pneumonia 1 Hyperplastic alveolar epithelium 2 Thickened alveolar walls with chronic inflammatory infiltration 3 Neutrophils in alveoli j0305257 Pneumoconiosis û an occupational and restrictive lung disease caused by the inhalation of specific dust û û sequels: inert (simple), fibrous, allergic, neoplastic û û high fibrogenicity of cristalline silica dust and asbestos û û 3 basic types: û ð coal-worker`s pneumoconiosis ð silicosis ð asbestosis j0305257 Silicosis û Chronic progressive pneumoconiosis û Silicone dioxide particles (0,2-2μm) toxic to macrophages – focal necrosis + release of fibrogenic factors - fibrosis ûX-ray – reticular fibrosis, nodules, diffuse fibrosis û lung insufficiency û cor pulmonale û û û ð j0305257 Silicosis û Gross (stages): ð reticular fibrosis ð ð silicotic nodules ð ð progressive massive fibrosis ð û Micro: ð nodules with concentric arrangement of hyalinized fibers and necrosis ð ð anthracophages in the periphery of the nodule ð ð emphysema in adjacent pulmonary tissue ð ð particles seen under polarized light j0305257 Silicotic nodule - lung silikosa 1. Fibrotic centre of the nodule 2. Emphysema 1 2 2 j0305257 Pulmonary silicosis Silica particles under polarized light j0305257 Granulomatous inflammations - Tuberculosis ûaetiology ðMycobacterium tuberculosis, M. bovis û ðspecial Ziehl-Neelsen stain •PCR more sensitive • ûdelayed-type hypersensitivity û (type IV. hypersensitivity) ðT cells-mediated immune memory response to TBC antigens (granulomas) j0305257 Tuberculosis – morphological features ûtbc granuloma – proliferative form ðhost resistance ðspecific granulation tissue: epithelioid macrophages + Langhans giant cells ð ûtbc exsudate – exsudative form (meningitis) ðallergy ðserofibrinous exsudate + Orth cells (macrophages) û +caseification ðcheese-like, caseous necrosis – sensibilization? û +colliquation (liquefaction) ðafter release of proteolytic enzymes by neutrophils û +calcification j0305257 Tbc granuloma 1caseous necrosis 2epithelioid macrophages 3Langhans giant cells 4lymphocytes 5 1 2 2 3 4 3 j0305257 Langhans giant cells j0305257 Caseous necrosis poprašková nekróza, 400x.jpg j0305257 Sarcoidosis û chronic granulomatous inflammatory disease of unknown aetiology û û affected tissue: ð mediastinal lymph nodes, lungs, skin, eye ð granulomas can affect any organ ð û small regular granulomas similar to TBC granulomas, but without caseous necrosis, fibrosis usually more pronounced û cytoplasmic bodies of Langhans giant cells, not specific: ð asteroid inclusions ð Schaumann bodies û û dg. per exclusionem – necessary elimination of TBC, fungal infection etc. j0305257 Sarcoidosis sarkoidóza-plíce1, 100x.jpg j0305257 Pulmonary chondrohamartoma û hamartoma? benign tumor? û û incidental X-ray finding û û differential diagnosis x malignant tumors important! û j0305257 Pulmonary chondrohamartoma û Gross: ð whitish yellow ð well demarcated ð lobular structure ð û Generally formed of mixture of homologous non-organised afunctional tissues : ð cartilage ð connective tissue ð fat ðtubular structures with epithelium û j0305257 Pulmonary chondrohamartoma chondrohamartom 20x 01 1.Cartilage 2.Fat tissue 3.Tubular structures with respiratory epithelium 1 2 3 j0305257 Pulmonary chondrohamartoma chondrohamartom 100x 02 Chondrocytes j0305257 Pulmonary chondrohamartoma chondrohamartom 100x 03 1. Cartilage 2. Fat tissue 3. Connestive tissue 4. Tubular structures 1 2 3 4 j0305257 Malignant lung tumors û Primary epithelial tumors – carcinomas ðSquamous cell ðSmall cell (undifferentiated neuroendocrine ca) ðAdenocarcinoma ðLarge cell undifferentiated carcinoma ðOther types (carcinoid tumors, adenosquamous ca, salivary gland tumors) û Primary mesenchymal tumors – sarcomas û Lymphoproliferative neoplasias û Metastatic tumors j0305257 Bronchogenic carcinoma û Very common primary malignancy û 5 year survival 5 – 7 % û 4 – 7 decenium, more commonly males û Clinical symptoms: late ðweight loss, chronic cough, haemoptysis, dyspnoea, chest pain, paraneoplastic syndromes (ACTH, ADH, PTH) û j0305257 Bronchogenic carcinoma û incidence: ð in CZE males 100/100 000 (the most common malignancy of men), ð females 25/100 000 (the 3rd most common malignancy of women, ↑ tendency) ð û aetiology: ð smoking • generally 20X higher risk in smokers • 20 cigarettes/day = 20 years, 40 cigarettes/day = 10 years... ð asbestos, Hg, Ni, As ð ionization ð radioactive radon ð dust particles ð familial predisposition û j0305257 Bronchogenic carcinoma û local complications: ð depends on the localization of the tumor: •lung collapse, bronchiectasis, bronchopneumonia, gangrene •widespread necrosis (more extensive in squamous cell ca) –destruction of vascular wall by tumor –fatal bleeding û clinical types: ð small cell lung carcinoma (SCLC) ð non-small cell lung carcinoma (NSCLC) j0305257 Neuroendocrine carcinomas ûNeuroendocrine differentiation – typical organoid growth pattern, neurosecretory granules, may be paraneoplastic syndromes – aberrant production of peptide hormones ûWell-differentiated neuroendocrine tumor, G1 – NET G1, carcinoid, i. e. in GIT, bronchi … ûModerately differentiated n. t., NET G2 – atypical carcinoid, ûNeuroendocrine tumor NET G3 û ûNeuroendocrine carcinoma – variable cell size, most common small cell carcinoma j0305257 Small cell lung carcinoma û undifferentiated (high grade) neuroendocrine tumor û û 20 % of all bronchogenic carcinomas û û associated with smoking û û localized in lung hilus û û early metastatic spread, widespread dissemination ð lymphatic and hematogenous (LN, liver, brain, bones, kidney, adrenals, …) û j0305257 Small-cell lung carcinoma û histologic types: ðsmall cell („oat cell carcinoma“) ð intermediate (now included into small cell type) ðcombined ð û Micro: ð small cells with scant cytoplasm (size < 3 lymphocytes) ð small round - elongated dark blue nuclei without obvious nucleoli (oat cell carcinoma) ð solid growth ð neurosecretory granules in cytoplasm • chromogranin, synaptophysin j0305257 Small-cell lung carcinoma 1 1 1 14_02 1 Peribronchial and perivascular infiltration 2 Infiltration of lymph nodes in hilus 3 Bronchus 4 Vessels 1 1 2 3 4 j0305257 Small-cell lung carcinoma malobb ca 100x 1. Solid small cell infiltration 2. Necrosis 3. Fibrous stroma 3 1 2 j0305257 Small-cell lung carcinoma malobb ca 200x 1. Solid small cell infiltration 2. Fibrous stroma 2 1 j0305257 Non-small cell lung carcinoma û squamous cell carcinoma û adenocarcinoma ð adenocarcinoma in situ ð minimally invasive: • non-mucinous • mucinous • mixed ð invasive: • lepidic • acinar • papillary • micropapillary • solid û large cell lung carcinoma û other, incl. mixed j0305257 Squamous cell carcinoma û male 40%, female 20% û strongly associated with smoking û typical perihilar localisation (central>peripheral) û commonly slow progression from squamous metaplasia – dysplasia – ca in situ ðlate metastases û Micro: ð squamous cell carcinoma of common type • polygonal shaped cells in solid nests, keratin pearls, cell junctions ð variable differentiation j0305257 Image059 copy j0305257 Squamous-cell lung carcinoma 11_01L 11_01R 1. Segmental bronchus 2. Tumor 1 1 2 2 j0305257 Squamous cell lung carcinoma 1103S2 11_03 1. Tumor localized in the periphery 2. Central necrosis 1 2 1. Tumor in bronchus 2. Segmental bronchus 2 1 j0305257 Squamous cell carcinoma spinaliom02 1.Solid nests of malignant keratinocytes 2.Keratin pearls 3.Stroma of the tumor 1 2 3 j0305257 Squamous cell carcinoma 02444-1 1.Tumor foci 2.Monocellular keratinization 1 2 j0305257 Squamous-cell carcinoma spinaliom04 1.Cell junctions 2.Nucleus with prominent nucleoli 1 2 j0305257 Adenocarcinoma û male 20%, female 40%; û û most cases in smokers, but the most common type in non-smokers û û typically localized in the periphery, subpleural ð late symptoms !!! Commonly accidental finding on X-ray/CT ð û formerly used term: ð bronchioloalveolar adenocarcinoma (BAC) no more in use (but still present in WHO classification of lung tumors) j0305257 Adenocarcinoma û classification: ð Adenocarcinoma in situ - AIS (size ≤3 cm): • non/mucinous (earlier BAC), • mucinous • mixed • no stromal/vascular/pleural invasion present • ð Minimally invasive ACA (size ≤3 cm and ≤ 5 mm invasion): idem • apart of lepidic growth other types of spread (papillary, solid….) or stromal invasion present • no vascular/pleural invasion present – ð Invasive ACA: • Lepidic • Acinar • Papillary • Micropapillary • Solid j0305257 Adenocarcinoma 12_01 1 Tumor localized in apex of the lung 2 Pigmentation inside the tumor 3 Emphysematous parenchyma 1 2 3 j0305257 Adenocarcinoma j0305257 Adenocarcinoma P0008 1. Structures of adenocarcinoma 2. Normal pulmonary parenchyma 1 2 j0305257 Adenocarcinoma P0009 1 2 1. Structures of adenocarcinoma 2. Normal pulmonary parenchyma j0305257 Adenocarcinoma P0001 1 2 1. Structures of adenocarcinoma 2. Normal pulmonary parenchyma j0305257 Adenocarcinoma P0002 Structures of an acinary and papillary formed adenocarcinoma j0305257 Adenocarcinoma P0010 Cytology of malignant cells - anisocytosis and anisokaryosis j0305257 Adenocarcinoma P0003 Cytology of malignant cells - anisocytosis and anisokaryosis j0305257 AIS/minimally invasive ACA non/mucinous (earlier BAC) 20x100 1 Normal alveolar walls 2 Alveolar walls with tumor cells 1 2 j0305257 AIS/minimally invasive ACA non/mucinous (earlier BAC) 20x400 1 Alveolar septum 2 Tumor 3 Malignant cells 1 2 3 j0305257 Large cell lung carcinoma û undifferentiated non-small cell carcinoma û û Micro: ð atypical pleomorphic cells ð ð absent features of small cell carcinoma, adenocarcinoma or squamous cell carcinoma j0305257 Large cell lung carcinoma 15_02 1 Necrosis 2 Bronchus 1 1 2 j0305257 Large cell lung carcinoma P0006 1. Pleomorphic tumor cells 2. Necrotic area 1 2 2 j0305257 Large cell lung carcinoma P0007 1. Pleomorphic tumor cells with prominent nucleoli 2. Necrotic area 2 1 j0305257 Mesothelioma ûprimary pleural tumor ûby far less common than secondary metastases of other tumors ûmostly malignant ûrisk factor: chronic exposition to asbestos ûGross: ð localized form ðdiffuse form ûMicro: ðepithelioid, sarcomatoid, biphasic, desmoplastic û