Category Archives: Lung

Chronic Bronchitis

Chronic bronchitis

Chronic bronchitis definition

·    Persistent cough with sputum production for at least 3 months in 2 consecutive years, in the absence of any other identifiable cause

Chronic bronchitis histology

·    Chronic inflammation of the airways (predominantly lymphocytes)

·    Enlargement of mucus-secreting glands of the trachea and bronchi

·    Ratio of thickness of mucus gland layer to ratio of wall thickness between epithelium and cartilage (Reid index) is >0.4

·    Squamous metaplasia and dysplasia of bronchial epithelium

·    Marked narrowing of bronchioles due to goblet cell metaplasia, mucus plugging, chronic inflammation and fibrosis

·    Clusters of pigmented alveolar macrophages may be seen

·    Obliteration of the lumen due to fibrosis (bronchiolitis obliterans) may be seen in severe cases

Chronic bronchitis pathology

·    Chronic irritation of bronchiolar and bronchial epithelium secondary to:

o    Tobacco smoke

o    Grain

o    Cotton

o    Silica dust

o    Air pollutants (sulfur dioxide, nitrogen dioxide)

·    Bacterial and viral infection are acute exacerbators of the disease

Longstanding severe chronic bronchitis changes

Hyperemia, edema, and swelling of mucous membranes

Excessive mucinous to mucopurulent layering of the epithelial surfaces

Heavy casts of secretions and pus filling bronchi and bronchioles

Evidence of cor pulmonale and cardiac failure with increase in right ventricular thickness, right atrial thickness and heart weight

Evidence of pulmonary hypertension with pulmonary artery atherosclerosis, thickening and luminal narrowing of pulmonary arterioles

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Malignant mesothelioma types

Malignant mesothelioma types

Malignant mesothelioma histologic classification

•    Epithelioid

•    Sarcomatoid

•    Mixed

•    Desmoplastic

•    Lymphohistiocytoid

•    Small cell variant

•    Squamous differentiation

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Malignant Mesothelioma Immunohistochemistry Electron Microscopy

Malignant Mesothelioma

Malignant mesothelioma histochemical, immunohistochemistry and electron microscopy ultrastructural features helpful in the differential diagnosis from metastatic adenocarcinoma

•    Histochemical

o    Mesothelioma: Alcian blue and colloidal iron positive; Alcian blue-hyaluronidase negative

o    Metastatic adenocarcinoma: Mucicarmine, PAS positive

•    Immunohistochemistry

o    Mesothelioma: Calretinin, CK5/6, thrombomodulin, WT-1, vimentin

o    Metastatic adenocarcinoma: CEA, BerEP4, B72.3, MOC-31, CD15, Bg8, TTF-1

•    Electron microscopy

o    Mesothelioma: Long numerous and slender microvilli (ratio:diameter of 15:1) with abundant tonofilaments, but absent microvillous rootlets and lamellar bodies

o    Metastatic adenocarcinoma: Short, plump microvilli, less numerous

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Diffuse Pulmonary Hemorrhage

Diffuse Pulmonary Hemorrhage

Associated conditions

•    Goodpasture syndrome

•    Wegener granulomatosis

•    Hypersensitivity angiitis

•    SLE

•    Idiopathic pulmonary hemosiderosis

Microscopic findings

•    Focal necrosis of alveolar walls

•    Intra-alveolar hemorrhage

•    Intra-alveolar hemosiderin-laden macrophages

•    Fibrous thickening of septae, type II pneumocyte hypertrophy, organization of blood in alveolar spaces

•    Capillaritis, scattered, poorly-formed granulomas

Prognosis

Idiopathic pulmonary hemosiderosis

o    Clinical benefit from corticosteroid therapy has been reported, however long-term benefit is unlikely

o    Mean length of survival is 3-5 years; adults have better prognosis than children

o    25% are free of disease after first episode; another 25% are free of active disease, but have persistent dyspnea and anemia; another 25% have persistent active disease that leads to fibrosis and severe restrictive lung disease; the remainder have unresponsive disease with repeated massive hemorrhage and early death from respiratory failure

Goodpasture syndrome

o    Treatment with plasmapheresis, corticosteroids and cytotoxic drugs is effective

o    Studies have shown 50% survival at 2 years (majority of deaths due to pulmonary hemorrhage with infection within the first year)

o    Oligoanuric renal failure reduces survival to 50% at 6 months

Wegener granulomatosis

o    Untreated, the disease course is malignant with 80% dying within first year; may be reduced to 37% with treatment
References: Robbins & Cotran Pathologic Basis of Disease, Seventh Edition

by: Vinay Kumar, Nelso Fausto, Abul Abbas

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Acute Respiratory Distress Syndrome

Acute Respiratory Distress Syndrome (ARDS)

Causes

•    Infection

o    Sepsis

o    Diffuse pulmonary infections (viral, Mycoplasma, Pneumocystis, military TB)

o    Gastric aspiration?

•    Physical/Trauma

o    Mechanical trauma (including head injuries)

o    Pulmonary contusions

o    Near-drowning

o    Fractures with fat embolism

o    Burns

o    Ionizing radiation

•    Inhaled irritants

o    Oxygen toxicity

o    Smoke

o    Irritant gases and chemicals

•    Chemical injury

o    Heroin/methadone overdose

o    ASA

o    Barbiturate overdose

o    Paraquat

•    Haematologic conditions

o    Multiple transfusions

o    DIC

•    Pancreatitis

•    Uremia

•    Cardiopulmonary bypass

•    Hypersensitivity reactions

•    Organic solvents

•    Drugs

Pathogenesis

•    Due to diffuse damage to the alveolar capillary walls

•    Initial injury is to capillary endothelium (usually) or alveolar epithelium (less often)

•    Leads to increased vascular permeability, alveolar flooding and loss of diffusion capacity and widespread surfactant abnormalities secondary to damage of type II pneumocytes

•    The exudate and diffuse tissue destruction that occurs cannot be resolved and organization with scarring results in chronic disease

•    As early as 30 minutes after the initial insult, IL-8 synthesis by macrophages increases.  This, with IL-1 and TNF leads to pulmonary microvascular sequestration and activation of neutrophils which are thought to play an important role in ARDS

•    Activated neutrophils release oxidants, proteases, PAF, and leukotrienes that damage tissue and maintain the inflammatory cascade.  Release of macrophage inhibitory factor sustains the inflammatory response.

Histological features

•    Congestion, interstitial and intra-alveolar edema, fibrin deposition and inflammation

•    The alveoli are lined by hyaline membranes (consisting of fibrin-rich edema mixed with cytoplasmic and lipid remnants of necrotic cells).

•    Proliferation of type II pneumocytes seen in organizing stage

•    Organization of fibrin exudate with intra-alveolar fibrosis; alveolar septal thickening secondary to deposition of collagen and proliferation of interstitial cells

•    May see superimposed bronchopneumonia

References: Robbins & Cotran Pathologic Basis of Disease, Seventh Edition
by: Vinay Kumar, Nelso Fausto, Abul Abbas

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Wegeners Granulomatosis

Wegener’s Granulomatosis

Clinical features

•    Persistent pneumonitis with bilateral nodular and cavitary infiltrates

•    Chronic sinusitis

•    Mucosal ulcerations of the nasopharynx

•    Evidence of renal disease

•    Skin rashes

•    Myalgias

•    Articular involvement

•    Mononeuritis/polyneuritis

•    Fever

Findings in kidney

•    Focal necrotizing glomerulonephritis

•    Crescentic glomerulonephritis (diffuse)

Other organs that can be involved

•    Lungs

•    Upper respiratory tract (ear, nose, sinuses and throat)

•    (Eye, skin, heart)

Positive blood test

•    c-ANCA

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Lung Carcinoma

Lung Carcinoma

Lung Cancer

Most common lung cancer histologic types

•    Squamous cell carcinoma
•    Adenocarcinoma
•    Small cell carcinoma
•    Large cell carcinoma

Electron microscopy features for lung cancers

•    Squamous cell carcinoma
o    Desmosomes seen
o    Cytoplasmic tonofilaments also seen
•    Adenocarcinoma
o    May exhibit mucin granules
o    Luminal microvilli
•    Small cell carcinoma
o    Dense neurosecretory granules (100 nm diameter)
o    Scant cytoplasm, sparse organelles

Prognostic factors

•    Tumour size
•    Tumour histological type
•    Invasion of visceral and or parietal pleura
•    Presence of obstructive pneumonitis
•    Lymph node involvement
•    Involvement of main bronchus
•    Presence/absence of malignant effusion
•    Involvement of chest wall, diaphragm, pericardium, mediastinal pleura, mediastinum, heart, great vessels
•    Vascular invasion (arteries, veins)
•    Involvement of margins
•    Presence of separate tumour nodules

Immunohistochemistry stains that differentiate lung carcinoma from metastatic colon carcinoma

•    TTF-1
•    CK20

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Emphysema

Emphysema

1.    Disruption in balance between proteases (elastase) and anti-proteases in favour of the former (protease-anti-protease theory).

2.    Can occur in smoking due to influx of neutrophils and macrophages within terminal bronchioles and subsequent release of  proteases (neutrophil elastase, cathepsin G, proteinase 3, macrophage elastase, matrix metalloproteinases).  Release of ROS from neutrophils inhibits alpha-1-antitrypsin, thus swaying balance in favour of proteases.

3.    Smoking also thought to disrupt oxidant-anti-oxidant balance.  Smoke contains ROS which depletes natural anti-oxidants (superoxide dismutase, glutathione) and recruits neutrophils that also release ROS.  AAT is also inhibited by ROS, which increases tissue damage)

4.    AAT deficiency also leads to emphysema since the protease-anti-protease balance is shifted towards the proteases.

Emphysema Types

1.    Centriacinar

2.    Panacinar

3.    Irregular

4.    Distal acinar/Paraseptal

5.    Bullous

6.    Interstitial

Eosinophils in pleural effusion causes

1.    Pneumothorax

2.    Parasites

3.    Hypersensitivity/Allergic reaction

4.    Drugs

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Mesothelioma

Mesothelioma

Cytological features

1.    Clusters of cells with “scalloped” edges

2.    Cells are larger than non-neoplastic mesothelial cells, but still demonstrate “windows”, and dense perinuclear cytoplasm with peripheral “halo”

3.    Prominent nucleoli

Electron microscopy findings

1.    Long, thin, branching microvilli with a length:diameter ratio of 15:1

2.    Numerous bundles of tonofilaments

Carcinoma versus Mesothelioma Immunohistochemistry

Antibody    Mesothelioma    Adenocarcinoma

Calretinin             +                             -

CK 5/6                  +                             -

Thrombomodulin (?)    +                   -

CEA                          -                         +

TTF (for lung adenoca.)    -             +

BerEP4                         -                     +

CD15                              -                    +

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Cystic fibrosis

Cystic fibrosis

Cystic fibrosis pathogenesis

Mutation of CFTR (most often ΔF508)

In sweat duct epithelium, dysfunction of the Cystic fibrosis transmembrane conductance regulator (CFTR) causes decrease in reabsorption of sodium chloride via ENaC (epithelial sodium channel), resulting in hypertonic sweat (“salty sweat”) as normally, ENaC absorbs chloride ions in sweat duct epithelium.

In respiratory and intestinal epithelium, dysfunction of CFTR causes loss or decreased chloride release into the lumen.  Sodium absorption is increased via ENac and results in net water absorption from the lumina of these systems, causing defective mucociliary function in the lungs and the accumulation of viscous secretions in the lungs and the intestines.

CFTR also mediates bicarbonate transport, so some mutations of CFTR can cause a decreased luminal pH, due to absence of bicarbonate ions.  This can result in increased mucin precipitation and plugging of ducts, increased bacterial adherence to plugged mucin and pancreatic insufficiency.

Gross lung findings

Distension of bronchioles with thick mucus (mucus plugging)

Bronchiectasis

Lung abscesses

Pneumonia (consolidation)

Cystic Fibrosis Extrapulmonary Lesions

Chronic sinusitis

Nasal polyps

Salivary gland abnormalities (plugging of ducts, squamous metaplasia, gland atrophy, fibrosis)

Pancreatic insufficiency (malabsorption, steatorrhea), acute/chronic pancreatitis

Meconium ileus

Biliary cirrhosis

Absent vas deferens, azoospermia

Organisms that cause lung infections in Cystic Fibrosis patients

Staphylococcus aureus

Pseudomonas aeruginosa

Haemophilus influenzae

Burkholderia cepaciae

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