Pathology of lung, pleura and upper airways Assoc. Professor Jan Laco, MD, PhD

Pathology of lung, pleura and Pathology of lung, pleura and upper airways upper airways

Assoc. Professor Jan Laco, MD, PhD

SummarySummary

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

AtelectasisAtelectasis

= inadequate expansion of airspaces (collapse) ventilation - perfusion imbalance – hypoxia

1. resorption atelectasis– 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

SummarySummary


Obstructive lung diseasesObstructive lung diseases

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

3. bronchiectasis 4. cystic fibrosis

Bronchial asthmaBronchial asthma

= 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


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


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

EmphysemaEmphysema

= 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

EmphysemaEmphysema

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

EmphysemaEmphysema

complications– respiratory failure– pulmonary hypertension right-sided heart failure

related conditions– compensatory emphysema– senile emphysema / hyperinflation– obstructive emphysema– mediastinal emphysema

Chronic bronchitisChronic bronchitis

= persistent productive cough for 3 consecutive months in 2 consecutive years

smoking, air pollutantsseveral forms:

– simple CB– mucopurulent CB– asthmatic CB– obstructive CB


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


complications– pulmonary hypertension– respiratory failure– recurrent infections– ? bronchogenic carcinoma

BronchiectasisBronchiectasis

= permanent bronchial / bronchiolar dilation due to wall components destruction

persistent cough + mucopurulent / fetid sputum 1. bronchial obstruction

– tumors, foreign bodies, mucous plugs 2. congenital conditions

– cystic fibrosis, Kartagener syndrome 3. supurative / necrotizing pneumonias

– Staphylococcus aureus– Klebsiella spp.

BronchiectasisBronchiectasis

obstruction + chronic infection wall damage wall weakening wall dilation

grossly - dilated distal bronchi / bronchioles + pus microscopically

– surface ulcerations + mixed inflammation– peribronchial fibrosis

complications:– lung abscess– obstructive ventilatory defects– metastatic brain abscess– AA amyloidosis

SummarySummary


Restrictive lung diseasesRestrictive 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 Acute respiratory distress syndrome (ARDS)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)


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)


microscopically - proliferative phase– pneumocytes II proliferation + hyaline

membranes phagocytosis (macrophages)– P II differentiate into pneumocytes I – interstitial fibroblasts proliferation interstitial

fibrosis = honeycomb lung


clinical course– !!! mortality 30-40% !!!– normal respiratory function within 6-12 months– diffuse interstitial fibrosis

Sudden Infant Death Sudden Infant Death SyndromeSyndrome

„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

SarcoidosisSarcoidosis

= 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 - distributionSarcoidosis - 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 courseSarcoidosis – 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

SummarySummary


Pulmonary hypertensionPulmonary 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 hypertensionPulmonary hypertension- morphology- morphology

1. main elastic arteries– atheromas ~ ATH

2. medium-sized muscular aa.– myointimal cells proliferation lumen

narrowing3. arterioles

– medial hypertrophy / thickening– plexiform lesions, fibrinoid necroses

SummarySummary


PneumoniasPneumonias

= 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

BronchopneumoniaBronchopneumonia

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 pneumoniaLobar 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

PneumoniaPneumonia- complications- complications

1. lung abscess– 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 pneumoniaAtypical 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

TuberculosisTuberculosis

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 TBCPrimary TBC

previously unexposed (unsensitized) personGhon 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 coursePrimary 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 TBCSecondary 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

SummarySummary


Lung carcinomaLung carcinoma

primary x secondary (metastases)95 % bronchogenic carcinoma

– bronchial epithelium

5% miscellaneous– carcinoid, bronchial glands, mesenchyma

benign - hamartomas

Bronchogenic carcinomaBronchogenic 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%)


advanced stage + metastases – symptoms chronic cough, hoarseness, chest pain Pancoast tumors – upper lobe apex

– branchial plexus invasion– sympathetic plexus invasion – Horner syndrome

paraneoplastic syndromes– hypercalcemia – PTH-related peptide– Cushing syndrome - ACTH– SIADH - ADH– neuromuscular syndromes – myasthenic syndrome– hematologic – NBTE, DIC

Squamous cell carcinomaSquamous 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

AdenocarcinomaAdenocarcinoma

peripheral location, in lung scarsslow growth x early metastasesatypical adenomatous hyperplasiaMi: solid x acinar x papillary

– bronchioloalveolar carcinoma growth along preexisting structures NO destruction

Small cell carcinomaSmall cell carcinoma

= poorly differentiated neuroendocrine Cacentral location + early metastasesMi: 2x than lymphocytes, scant cytoplasm +

mitotic ratehighly aggressive tumor


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

SummarySummary


Pleural effusionPleural effusion

1. hydrothorax – transudate– congestive heart failure

2. pleuritis + exudate– pulmonary infections + TBC– neoplasms (lung, mesothelioma)– pulmonary infarction– viral pleuritis

complications– suppurative, fibrinous pleuritis organization

adhesions + calcification

Other pleural conditionsOther 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)

MesotheliomaMesothelioma

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

SummarySummary


Acute infectionsAcute infections

1. „common cold“– rhinoviruses, coronaviruses, influenza virus– self-limiting diseases

2. acute tonsilitis– beta-hemolytic Streptococci, adenoviruses– peritonsillar abscess– post-streptococcal glomerulonephritis– acute rheumatic fever

3. herpangina– Coxsackievirus A

4. infectious mononucleosis (EBV)

Acute infectionsAcute 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 tumorsNasopharyngeal tumors

1. squamous cell carcinoma2. lymphoepithelial carcinoma

– malignant– EBV, China– 5year survival: 50%

3. malignant lymphomas - DLBCL4. angiofibroma

– young boys– benign x locally destructive + bleeding

Laryngeal tumorsLaryngeal tumors

1. vocal cord nodules– heavy smokers, singers, teachers– true vocal cords, 0.5 cm

2. squamous papilloma– benign– true vocal cords– soft excrescence, 1cm– children – multiple

juvenile laryngeal papillomatosis HPV 6, 11 spontaneous regress

Laryngeal tumorsLaryngeal tumors

3. laryngeal carcinoma (2% of all carcinomas)– > 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

Documents

Pathology of lung, pleura and upper airways Assoc. Professor Jan Laco, MD, PhD