Pathology of lung, pleura and
upper airways
Assoc. Professor Jan Laco, MD, PhD
Summary
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1. Atelectasis
2. Obstructive lung diseases
3. Restrictive lung diseases
4. Vascular lung diseases
5. Pulmonary infections
6. Lung tumors
7. Pleural lesions
8. Lesions of upper RT
Atelectasis
= inadequate expansion of airspaces (collapse)
 ventilation - perfusion imbalance – hypoxia
 1. resorption atelectasis
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–
–
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obstruction of airway – air resoption
mucous / mucopurulent plug - bronchial asthma
foreign body aspiration
bronchogenic carcinoma, enlarged LN (TBC,…)
 2. compression atelectasis
– pleural effusions, pneumothorax, ascites
Summary
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1. Atelectasis
2. Obstructive lung diseases
3. Restrictive lung diseases
4. Vascular lung diseases
5. Pulmonary infections
6. Lung tumors
7. Pleural lesions
8. Lesions of upper RT
Obstructive lung diseases
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 resistance due to parcial / complete obstruction
at any level
TLC + FVC normal
x  expiratory flow rate (FEV1)
1. bronchial asthma
2. chronic obstructive pulmonary disease
– 2a. emphysema
– 2b. chronic bronchitis / bronchiolitis
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3. bronchiectasis
 4. cystic fibrosis
Bronchial asthma
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= episodic reversible bronchospasm
basis: tracheobronchial hyperreactivity  chronic
inflammation of bronchi
incidence: 7-10% children + 5% adults
early onset
dyspnea, cough, wheezing ~ hours
expiratory difficulty  lung hyperinflation
status asthmaticus ~ days  fatal
Bronchial asthma
1. extrinsic asthma
– type I hypersensitivity reaction to extrinsic
antigens
– most common, familial predisposition
– diet proteins, herbal pollen, animal hair, mites
2. intrinsic asthma
– drugs, viral infection
Bronchial asthma
 grossly: bronchial occlusion by thick mucus plug
 microscopically:
– mucus
 Curshmann spirals, eosinophils, Charcot-Leyden crystals
– bronchial wall
 edema + hyperemia
 inflammation – eosinophils, basophils, macrophages,
lymphocytes (Th2 subset)
 hypertrophy of submucosal mucous glands
 thickened basement membrane
 hypertrophy / hyperplasia of SMCs
Emphysema
= permanent enlargement of airspaces distal to
terminal bronchioles due to destruction of their
walls
 smoking
 pathogenesis
– oxidant-antioxidant imbalance
– protease-antiprotease imbalance
 α1-antitrypsin deficiency
 dyspnea + prolonged expiration
 barrel-chested patients
Emphysema
 1. centriacinar emphysema
– only respiratory bronchioles affected
– upper lobes
– smoking
 2. panacinar emphysema
– respiratory bronchioles + alveoli affected
– lower lobes
– α1-antitrypsin deficiency
 G: pale voluminous areas
 Mi: thining / destruction of alveolar walls  large
airspaces
Emphysema
 complications
– respiratory failure
– pulmonary hypertension  right-sided heart failure
 related conditions
–
–
–
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compensatory emphysema
senile emphysema / hyperinflation
obstructive emphysema
mediastinal emphysema
Chronic bronchitis
= persistent productive cough for 3
consecutive months in 2 consecutive years
 smoking, air pollutants
 several forms:
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simple CB
mucopurulent CB
asthmatic CB
obstructive CB
Chronic bronchitis
 basis: hypersecretion / hypertrophy of bronchial
mucous glands + inflammation
 grossly
– mucosal hyperemia + edema
– mucous / mucopurulent secretion in lumen
 microscopy
– enlargement of mucus-secreting glands (Reid index)
– squamous metaplasia
– mononuclear inflammation
 bronchioles
– goblet cells metaplasia + wall fibrosis
Chronic bronchitis
complications
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pulmonary hypertension
respiratory failure
recurrent infections
? bronchogenic carcinoma
Bronchiectasis
= permanent bronchial / bronchiolar dilation due to
wall components destruction
 persistent cough + mucopurulent / fetid sputum
 1. bronchial obstruction
– tumors, foreign bodies, mucous plugs
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2. congenital conditions
– cystic fibrosis, Kartagener syndrome
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3. supurative / necrotizing pneumonias
– Staphylococcus aureus
– Klebsiella spp.
Bronchiectasis
 obstruction + chronic infection  wall damage 
wall weakening  wall dilation
 grossly - dilated distal bronchi / bronchioles + pus
 microscopically
– surface ulcerations + mixed inflammation
– peribronchial fibrosis
 complications:
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–
–
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lung abscess
obstructive ventilatory defects
metastatic brain abscess
AA amyloidosis
Summary
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1. Atelectasis
2. Obstructive lung diseases
3. Restrictive lung diseases
4. Vascular lung diseases
5. Pulmonary infections
6. Lung tumors
7. Pleural lesions
8. Lesions of upper RT
Restrictive lung diseases
 reduced expansion of lung parenchyma
   FVC x FEV1 normal
 1. extra-pulmonary disorders
– severe obesity, kyphoscoliosis, neuromuscular diseases
 2. interstitial lung disorders
– acute
 acute respiratory distress sydrome (ARDS)
– chronic
 pneumoconioses
 sarcoidosis
 idiopathic pulmonary fibrosis
 hypersensitivity pneumonitis
Acute respiratory distress
syndrome (ARDS)
= acute dyspnea onset + hypoxemia + RTG
bilateral infiltrates + NO left-sided HF
= diffuse alveolar damage (DAD)
 direct lung injury
– pneumonia - viral
– aspiration
– pulmonary contusion, inhalation injury
 indirect lung injury
– sepsis, shock – „shock lung“
– uremia
– drug overdose (cytostatics)
Acute respiratory distress
syndrome (ARDS)
 epithelium + endothelium injury  alveolar
capillary membrane damage   vascular
permeability  alveolar flooding + surfactant
abnormalities
 grossly
– dark red + firm + airless + heavy lung ~ liver
 microscopically - acute phase
– capillary congestion + alveolar cells necrosis
– interstitial + alveolar edema + hemorrhage
– hyaline membranes (edema fluid + cell debries)
Acute respiratory distress
syndrome (ARDS)
microscopically - proliferative phase
– pneumocytes II proliferation + hyaline
membranes phagocytosis (macrophages)
– P II differentiate into pneumocytes I
– interstitial fibroblasts proliferation 
interstitial fibrosis = honeycomb lung
Acute respiratory distress
syndrome (ARDS)
clinical course
– !!! mortality 30-40% !!!
– normal respiratory function within 6-12 months
– diffuse interstitial fibrosis
Sudden Infant Death
Syndrome
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„sudden death of infant < 1 year + complete
autopsy does not reveal other cause of death“
1 to 700-1,000 liveborn
age: 2 - 4 months, boys (2 : 1)
crib death x night ~ day
winter (infection – trigger ???)
mother´s smoking
autopsy: big thymus + serosal petechiae
??? brain stem ganglia abnomalities
??? heart conductive system abnormalities
Sarcoidosis
= multisystemic disease with noncaseating
granulomas in many tissues and organs
 etiology – unknown (??? Th lymphocytes)
 younger adults, non-smokers
 familial clustering, Scandinavia
 hypercalcemia + hypercalciuria
 microscopy (dg. of exclusion)
– noncaseating granulomas + specific granulation tissue
– epithelioid + multinucleated cells
– Schaumann bodies + asteroid bodies
Sarcoidosis - distribution
 hilar LN (75-90%)
 lungs (90%)
– around bronchioles + venules + subpleural
 skin (25%)
– erythema nodosum (legs)
– lupus pernio (nose, cheeks, lips)
 eye + lacrimal glands (20-50%)
– iridocyclitis, retinitis, optic nerve involvement
 salivary glands (10%)
– xerostomia
 spleen + liver + bone marrow
Sarcoidosis – clinical course
 asymptomatic
 respiratory symptoms
– dyspnea, cough, …
 constitutional signs
– fever, fatique, weight loss…
 uveoparotid involvement = Heerfordt syndrome
 prognosis – unpredictable
– 70% - complete recovery
– 20% - lung dysfunction + visual impairment
– 10% progressive pulmonary fibrosis + cor pulmonale
Summary
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1. Atelectasis
2. Obstructive lung diseases
3. Restrictive lung diseases
4. Vascular lung diseases
5. Pulmonary infections
6. Lung tumors
7. Pleural lesions
8. Lesions of upper RT
Pulmonary hypertension
primary hypertension
– plexiform pulmonary arteriopathy
– pulmonary venoocclusive disease
secondary hypertension
– cardiac disease – L-to-R shunts, mitral stenosis
– lung diseases
chronic obstructive and restrictive diseases
recurrent thrombembolism
Pulmonary hypertension
- morphology
1. main elastic arteries
– atheromas ~ ATH
2. medium-sized muscular aa.
– myointimal cells proliferation  lumen
narrowing
3. arterioles
– medial hypertrophy / thickening
– plexiform lesions, fibrinoid necroses
Summary
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1. Atelectasis
2. Obstructive lung diseases
3. Restrictive lung diseases
4. Vascular lung diseases
5. Pulmonary infections
6. Lung tumors
7. Pleural lesions
8. Lesions of upper RT
Pneumonias
= infectious inflammation of lung
 1. comm.- acq. acute pneumonia (bacteria)
 2. atypical pneumonia (viruses, Mycoplasma, Chlamydia)
 3. nosocomial pneumonia (gram-negative rods)
 4. aspiration pneumonia (anaerobic oral flora)
 5. chronic pneumonia (TBC)
 6. necrotizing pneumonia / lung abscess
 anaerobic bacteria, S. aureus, K. pneumoniae
 7. pneumonia in immunocompromised host
 CMV, P. carinii, atypical Mycobacteria, fungi
Bronchopneumonia
 Streptococci, Staphylococci, H. influenzae
 from lower airways  alveoli
 grossly
– patchy inflammatory consolidation
– bilateral basal localization
– 3-4 cm, red to yellow patches
 microscopically
– suppurative inflammation in bronchi + bronchioles +
alveoli
Lobar pneumonia
 Streptococcus pneumoniae 1, 2, 3
 rapid spread within alveoli
 1. congestion - heavy, red, boggy
– alveolar edema + neutrophils
 2. red hepatization - liver-like consistency
– alveoli fulfilled by neutrophils, RBCs, fibrin
– fibrinous / fibrinopurulent pleuritis
 3. gray hepatization - dry, firm
– RBCs lysis + fibrin persistance
 4. resolution
Pneumonia
- complications
 1. lung abscess
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acute x chronic
bronchogenic – S. aureus, K. pneumoniae
x hematogenic (peripheral pyemia)
bronchopleural fistulas – pneumothorax + empyema
brain abscess + AA amyloidosis
 2. empyema
 3. lung fibrosis + pleural adhesions
 4. bacteremia
– meningitis, arthritis, infective endocarditis
Atypical pneumonia
 viruses (influenza, adenovirus, RSV, CMV)
 Chlamydiae, Rickettsiae
 grossly
– patchy x segmental x lobular, red-blue, congested areas
 microscopically
– alveolar septa – edema + mononuclear infiltrate
 prognosis
– complete recovery
– bacterial superinfection
– ARDS
Tuberculosis
 Mycobacterium tuberculosis
 Ziehl-Neelsen – acid-fast red rod
 inhalation  lungs
 T cells mediated immunity
– organism resistance
– tissue hypersensitivity – caseous necrosis
 caseating granulomas
– central caseous necrosis
– epithelioid cells + multinucleated giant cells (Langhans)
– T-lymphocytic rim
Primary TBC
previously unexposed (unsensitized) person
Ghon focus
– lung middle line + subpleural location
– 1-1.5 cm, gray-white lesion
Ghon complex: + TBC hilar LNitis
+ lympho / hematogenous dissemination
– under immune control
Primary TBC - further course
 1. healed lesions – fibrocalcific scar
 2. latent lesions (dormant TBC organisms)
 3. cervical LNitis („scrophula“)
 3. progressive primary TBC
– miliary („millet“) TBC - 2 mm, yellow-white
– pulmonary
 lymphatics – thoracic duct – venous circulation – right heart –
pulmonary a. – lungs
 pleural effusion, TBC empyema
– systemic
 pulmonary veins – left heart – systemic circulation
 liver, BM, spleen, adrenals, menings, kidneys, fall.t., epid.
Secondary TBC
 in previously sensitized person
 1. exogenous reinfection
 2. reactivation
– pulmonary TBC (from adenobronchial fistula)
 upper lobes apex
 cavitation – airways dissemination – progressive pulmonary
TBC
 bronchus erosion - endo-bronchial,-tracheal, laryngeal TBC
 blood vessel erosion – hemoptysis
 pulmonary + systemic miliary TBC
– isolated-organ metastasis (from primary TBC metast.)
 TBC meningitis, epinephritis, osteomyelitis, salpingitis
Summary
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1. Atelectasis
2. Obstructive lung diseases
3. Restrictive lung diseases
4. Vascular lung diseases
5. Pulmonary infections
6. Lung tumors
7. Pleural lesions
8. Lesions of upper RT
Lung carcinoma
primary x secondary (metastases)
95 % bronchogenic carcinoma
– bronchial epithelium
5% miscellaneous
– carcinoid, bronchial glands, mesenchyma
benign - hamartomas
Bronchogenic carcinoma
 very common, !!! smoking !!!
 peak incidence 55 – 65 years
M:F…2:1
 1. non-small cell lung carcinoma (70-75%)
 surgery
– squamous cell carcinoma (25-30%)
– adenocarcinoma (30-35%)
– large cell carcinoma (10-15%)
 2. small cell lung carcinoma (20-25%)
 chemotherapy +/- actinotherapy
 3. combined carcinoma (5-10%)
Bronchogenic carcinoma
 advanced stage + metastases – symptoms
 chronic cough, hoarseness, chest pain
 Pancoast tumors – upper lobe apex
– branchial plexus invasion
– sympathetic plexus invasion – Horner syndrome
 paraneoplastic syndromes
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hypercalcemia – PTH-related peptide
Cushing syndrome - ACTH
SIADH - ADH
neuromuscular syndromes – myasthenic syndrome
hematologic – NBTE, DIC
Squamous cell carcinoma
 central location in major bronchi
 local spread x later distant metastases
 bronchial epithelium
– squamous metaplasia – dysplasia – carcinoma in situ –
invasive carcinoma
 grey-white tumor mass + necroses
– lumen obstruction – atelectasis + infection
 Mi: squamous cell carcinoma + keratin pearls
Adenocarcinoma
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peripheral location, in lung scars
 slow growth x early metastases
 atypical adenomatous hyperplasia
 Mi: solid x acinar x papillary
– bronchioloalveolar carcinoma
 growth along preexisting structures
 NO destruction
Small cell carcinoma
= poorly differentiated neuroendocrine Ca
 central location + early metastases
 Mi: 2x than lymphocytes, scant cytoplasm +
 mitotic rate
 highly aggressive tumor
Bronchogenic carcinoma
 local spread
– lungs, mediastinum
– pericardium, pleura
 lymphatic nodes
– hilar, mediastinal, paratracheal
 distant metastases
– liver, brain, adrenals, bone
 !!! poor prognosis: 5-year survival 14% !!!
 biologic therapy – TKIs of EGFR and of ALK
Summary
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1. Atelectasis
2. Obstructive lung diseases
3. Restrictive lung diseases
4. Vascular lung diseases
5. Pulmonary infections
6. Lung tumors
7. Pleural lesions
8. Lesions of upper RT
Pleural effusion
 1. hydrothorax – transudate
– congestive heart failure
 2. pleuritis + exudate
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pulmonary infections + TBC
neoplasms (lung, mesothelioma)
pulmonary infarction
viral pleuritis
 complications
– suppurative, fibrinous pleuritis  organization 
adhesions + calcification
Other pleural conditions
 3. pneumothorax – air in pleural sac
– lung disease (emphysema, abscess, carcinoma)
– thoracic wall injury (rib fracture)
– complications
 mediastinum shift + lung compression
 4. hemothorax – blood in pleural sac
– thoracic aorta aneurysm rupture
 5. chylothorax – lymph in pleural sac
– obstruction of lymphatic ducts (mediastinal neoplasms)
Mesothelioma
 rare malignant tumor of mesothelial cells
 asbestos exposure + long latent period
 grossly
– lung ensheathed by yellow-white firm / gelatinous mass
+ pleural obliteration
– invasion into lung + thoracic wall
 microscopically
– epithelial + sarcomatoid + biphasic
 poor prognosis
Summary
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1. Atelectasis
2. Obstructive lung diseases
3. Restrictive lung diseases
4. Vascular lung diseases
5. Pulmonary infections
6. Lung tumors
7. Pleural lesions
8. Lesions of upper RT
Acute infections
 1. „common cold“
– rhinoviruses, coronaviruses, influenza virus
– self-limiting diseases
 2. acute tonsilitis
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beta-hemolytic Streptococci, adenoviruses
peritonsillar abscess
post-streptococcal glomerulonephritis
acute rheumatic fever
 3. herpangina
– Coxsackievirus A
 4. infectious mononucleosis (EBV)
Acute infections
5. acute epiglottitis !!!
– young children
– H. influenzae
– airway obstruction – tracheotomy x lethal
6. acute laryngitis
– air irritants, allergic
– diphtheria – pseudomembranous l. (aspiration)
– TBC
Nasopharyngeal tumors
1. squamous cell carcinoma
2. lymphoepithelial carcinoma
– malignant
– EBV, China
– 5year survival: 50%
3. malignant lymphomas - DLBCL
4. angiofibroma
– young boys
– benign x locally destructive + bleeding
Laryngeal tumors
 1. vocal cord nodules
– heavy smokers, singers, teachers
– true vocal cords, 0.5 cm
 2. squamous papilloma
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–
–
–
benign
true vocal cords
soft excrescence, 1cm
children – multiple
 juvenile laryngeal papillomatosis
 HPV 6, 11
 spontaneous regress
Laryngeal tumors
 3. laryngeal carcinoma (2% of all carcinomas)
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> 40 years
M:F…7:1
smoking + alcohol
95% squamous cell carcinomas
dysplasia  carcinoma in situ  invasive Ca
grey plaque  ulceration
glottic (60-75%) -  prognosis
supraglottic (25-40%) -  prognosis
subglotic (5%) -  prognosis