1. General Pathology
    2. 1. The Cell as a Unit of Health and Disease
    2. Cellular Response to Stress and Toxic Insults
    3. Inflammation and Repair
    4. Hemodynamic Disorders, Thromboembolic Disease, and Shock
    5. Genetic Disorders
    6. Diseases of the Immune System
    7. Neoplasia
    8. Infectious Diseases
    9. Environmental and Nutritional Diseases
    10. Diseases of Infancy and Childhood
  2. Systemic Pathology: Diseases of Organ Systems
    3. 11. Blood vessels
    12. The Heart
    13. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus
    14. Red Blood Cell and Bleeding Disorders
    15. The Lung
    16. Head and Neck
    17. The Gastrointestinal Tract
    18. Liver and Gallbladder
    19. The Pancreas
    20. The Kidney
    21. The Lower Urinary Tract and Male Genital System
    22. The Female Genital Tract
    23. The Breast
    24. The Endocrine System
    25. The Skin
    26. Bones, Joints, and Soft Tissue Tumors
    27. Peripheral Nerves and Skeletal Muscles
    28. The Central Nervous System
    29. The Eye
Systemic Pathology: Diseases of Organ Systems
15. The Lung
CONGENITAL ANOMALIES
Pulmonary hypoplasia
Image 1
Fig. Pulmonary hypoplasia
Pulmonary hypoplasia is the defective development of both lungs (one may be more affected than the other) resulting in decreased weight, volume, and acini for body weight and gestational age.
▢ Causes:
  1. Congenital diaphragmatic hernia
  2. Oligohydramnios
Foregut cysts
Image 1
Fig. Congenital Foregut
Cyst (CFC)
Foregut cysts arise from abnormal detachments of primitive foregut and most often located in the hilum or middle mediastinum.
▢ Classification:
❖ Bronchogenic foregut cyst:
◉ Microscopic: Ciliated pseudostratified columnar epithelium
◉ Wall contents:
  1. Bronchial glands
  2. Cartilage
  3. Smooth muscle
◉ Most common
❖ Oesophageal foregut cyst:
❖ Enteric foregut cyst:
Pulmonary sequestration
Image 1
Fig. Pulmonary sequestration
Pulmonary sequestration refers to a discrete area of lung tissue that
  1. lacks any connection to the airway system and
  2. has a abnormal blood supply arising from the aorta and its branches.
Extralobar sequestration
Intralobar sequestration
Site
External to the lungs
Within the lungs
Present in
Infants
Older children
Cause
  1. Recurrent localized infection
  2. Bronchiectasis
ATELECTASIS (COLLAPSE)
Image 1
Fig. Atelectas
Atelectasis refers either to incomplete expansion of the lungs (neonatal atelectasis) or to the collapse of the previously inflated lung, producing areas of relatively airless pulmonary parenchyma.
Resorption (Obstruction) atelectasis
Compression atelectasis
Contraction atelectasis
Cause
Complete obstruction of an airway caused by
  1. Excessive secretions (e.g., mucus plugs)
  2. Exudates within smaller bronchi may occurs in
    1. Bronchial asthma
    2. Chronic bronchitis
    3. Bronchiectasis
    4. Postoperative states
  3. Aspiration of foreign bodies
  4. Fragments of bronchial tumors
Accumulation of significant volumes of
  1. fluid (transudate, exudate or blood)
  2. tumor or
  3. air (pneumothorax)
Focal or generalized pulmonary or pleural fibrosis
Mediastinal shift
Towards the atelectatic lung
Away from the affected lung
PULMONARY EDEMA
Pulmonary edema is leakage of excessive interstitial fluid which accumulates in alveolar spaces caused either by hemodynamic disturbances or from direct increases in capillary permeability.
Hemodynamic pulmonary edema
▢ Causes:
❖ Increased hydrostatic pressure (Increased pulmonary venous pressure):
  1. Left-sided heart failure (common)
  2. Volume overload
  3. Pulmonary vein obstruction
❖ Decreased oncotic pressure (Less common):
  1. Hypoalbuminemia
  2. Nephrotic syndrome
  3. Liver disease
  4. Protein-losing enteropathies
❖ Lymphatic obstruction (rare):
Edema caused by Microvascular (Alveolar) injury
▢ Causes:
❖ Direct injury:
  1. Infections: bacterial pneumonia
  2. Inhaled gases: high concentration oxygen, smoke
  3. Liquid aspiration: gastric contents, near-drowning
  4. Radiation
❖ Indirect injury:
  1. Septicemia
  2. Blood transfusion related
  3. Burns
  4. Drugs and chemicals
    1. Chemotherapeutic agents (bleomycin)
    2. Other medications (Methadone, amphotericin)
    3. Heroin
    4. Cocaine
    5. Kerosene
    6. Paraquat
  5. Shock
  6. Trauma
Edema of Undetermined Origin
▢ Causes:
  1. High altitude
  2. Neurogenic (central nervous system trauma)
ACUTE LUNG INJURY AND ACUTE RESPIRATORY DISTRESS SYNDROME (DIFFUSE ALVEOLAR DAMAGE)
Acute Interstitial Pneumonia
OBSTRUCTIVE AND RESTRICTIVE LUNG DISEASES
Obstructive lung disease
Restrictive lung disease
Characteristics
Increase in resistance to airflow due to partial or complete obstruction at any level from the trachea and large bronchi to the terminal and respiratory bronchioles.
Reduced expansion of lung parenchyma and decrease total lung capacity.
Pulmonary function test
Decreased FEV1/FVC ratio (<0.7)
Normal FEV1/FVC ratio
Examples
  1. Asthma
  2. Chronic bronchitis
  3. Emphysema
  4. Bronchiectasis
OBSTRUCTIVE LUNG DISEASES
Emphysema
Chronic Bronchitis
Asthma
Bronchiectasis
CHRONIC DIFFUSE INTERSTITIAL (RESTRICTIVE) DISEASES
Fibrosing Diseases
Idiopathic Pulmonary Fibrosis
Nonspecific Interstitial Pneumonia
Cryptogenic Organizing Pneumonia
Pulmonary Involvement in Autoimmune Diseases
Pneumoconioses
Introduction
Definition
  1. Pneumoconioses encompass a group of fibrosing diseases of the lung resulting from exposure to organic and inorganic particulates, most commonly mineral dust.
  2. Initially it was used to describe the non-neoplastic lung reaction to inhalation of mineral dusts encountered in the workplace.
  3. But, now it has been proved that many pneumoconioses especially asbestosis increases the risk of mesothelioma by 1000 times and that of bronchogenic carcinoma by many times.
  4. So, pneumoconioses are also the pre-cancerous lesions.
Classification
On the basis of Etiology, it is classified into following types.
Pathogenesis
  1. The particles greater than 5μm are easily trapped in the upper respiratory passage in the mucus and are expelled out by mucocilliary actions.
  2. The particles lesser than 0.5μm nearly the size of air and thus are inhaled and exphaled along with air causing no damage to cells.
  3. So, the paricles between 1μm and 5μm are the one to get stuck in the lower respiratory passages, especially at the bifurcation of respiratory tree; and alveoli.
  4. These particles are engulfed by the macrophages of the lungs and are taken up to lymph nodes, where it presents the antigen to the lymphocytes.
  5. Thus the inflammatory reaction occurs in the lung parenchyma and along the lymphatic drainage.
graph TD 1["Inhalation"] 2["Particle of size >5μm"] 3["Easily trapped in the upper <br>respiratory passage in the mucus"] 4["Expelled out by mucocilliary actions"] 5["Particle of size <0.5μm"] 6["Nearly the size of air"] 7["Inhaled and exphaled along with air"] 8["Causes no damage to cell"] 9["Particle of size between 1μm and 5μm"] 10["get stuck in the lower <br>respiratory passages, especially at the <br>bifurcation of respiratory tree; and alveoli."] 11["engulfed by the macrophages of the lungs"] 12["taken up to lymph nodes"] 13["presents the antigen to the lymphocytes"] 14["inflammatory reaction occurs <br>in the lung parenchyma and <br>along the lymphatic drainage"] 1 --> 2 2 --> 3 3 --> 4 4 --> 8 1 --> 5 5 --> 6 6 --> 7 7 --> 8 1 --> 9 9 --> 10 10 --> 11 11 --> 12 12 --> 13 13 --> 14
Types
  1. Here we will talk many about the following three pneumoconiosis
    1. Coal Workers' Pneumoconiosis
    2. Silicosis
    3. Asbestosis
  2. The general pathogenesis of all of them are given above.
  3. Coal and Silica comes from the ground and affect the upper lobes or upper part of middle lobes of lung, where as Asbestos comes from upper surfaces like roofs of house and it affects the lower lobes of lungs.
Coal Workers' Pneumoconiosis
Pathogenesis
Same as common pathogenesis
graph TD 1["Anthracosis"] 2["Simple coal workers' pneumoconiosis"] 3["Complicated coal workers' pneumoconiosis (Progressive massive fibrosis)"] 1 --> 2 2 --> 3
Morphology
Anthracosis
  1. Inhaled carbon pigment is engulfed by alveolar or interstitial macrophages.
  2. These then accumulate in the connective tissue along the lymphatics including
    1. Pleural lymphatics
    2. Organized lymphoid tissue along the bronchi or in the lung hilus
Simple coal workers' pneumoconiosis
Gross
  1. Lesions are mostly localized in upper lobes or upper part of lower lobes.
  2. Coal macules of 1 to 2 mm in diameter.
  3. Larger coal nodules
Microscopic
  1. Coal macules
    • •
      It consists of carbon-laden macrophages.
  2. Coal nodules
    • •
      It contain a delicate network of collagen fibers.
  3. They are located primarily adjacent to respiratory bronchioles, the site of initial dust accumulation.
  4. In due course dilation of adjacent alveoli occurs, sometimes giving rise to centrilobular emphysema.
Complicated coal workers' pneumoconiosis/ Progressive massive fibrosis (PMF)
Gross
  1. Intense blackened scars ranging from 1 cm to 10 cm in diameter.
  2. They are usually multiple.
Microscopic
  1. It consists of dense collagen and carbon pigment.
  2. The center of lesion is often necrotic, most likely due to local ischemia.
Silicosis
Morphology
Gross
Simple nodules
At first tiny barely palpable, discrete pale to blackened (if coal dust is also present) nodules in the hilar lymph nodes and upper zones of the lungs is found.
Collagenous scars
As the disease progresses, these nodules coalesce into hard, collagenous scars.
Centrally softened and cavitary nodules
Some nodules may undergo central softening and cavitation due to superimposed tuberculosis or to ischemia.
Fibrotic lesions
Fibrotic lesions may also occur in the hilar lymph nodes and pleura.
Eggshell calcified nodule
Sometimes, thin sheets of calcification occur in the lymph nodes and are seen radiographically as calcium surrounding a zone lacking calcification.
Progressive massive fibrosis
As the disease continues to progress, expansion and coalescence of lesions may produce progressive massive fibrosis.
Microscopic
Silicotic nodules
It has a characteristic whorled appearance.
Center
It consists of concentric layers of hyalinized acellular collagen surrounded by a dense cellular capsule of connective tissue and collagen.
Periphery
Shows aggregates of mononuclear cells, mostly macrophages, lymphocytes and fibroblasts.
Polarized light microscopy may show birefringent silica particles in the center of silicotic nodule.
Pathogenesis
graph TD 1["Silica"] 2["Amorphous forms <br>- Biologically less active than crystalline silica"] 3["When Heavy lung burdens"] 4["Lesions"] 5["Crystalline forms <br>- They are highly fibrogenic."] 6["Quartz <br>- Quartz is most <br>commonly implicated."] 7["Cristobalite"] 8["Tridymite"] 9["Inhalation of silica particles."] 10["Phagocytosis of the particles by macrophages."] 11["Phagocytosed silica crystals activate the inflammasome."] 12["Release of inflammatory mediators, particularly IL-1 and IL-8."] 13["Formation of Fibrotic nodules."] 1 --> 2 2 --> 3 3 --> 4 1 --> 5 5 --> 6 6 --> 9 5 --> 7 7 --> 9 5 --> 8 8 --> 9 9 --> 10 10 --> 11 11 --> 12 12 --> 13
Asbestosis
Morphology
Gross
  1. Lesions are mostly localized in lower lobes or lower part of upper lobes.
  2. Diffuse pulmonary interstitial fibrosis
    1. Asebestosis is marked by diffuse pulmonary interstitial fibrosis.
    2. Early: Asbestosis begins as fibrosis around respiratory bronchioles and alveolar ducts and extends to involve adjacent alveolar sacs and alveoli.
    3. Later: The fibrous tissue distorts the architecture, creating enlarged airspaces enclosed within thick fibrous walls; eventually the affected regions become honeycombed.
    4. The pattern of fibrosis is similar to that seen in usual interstitial fibrosis, the only difference being the presence of numerous asbestos bodies.
Microscopic
  1. Asbestos bodies
    1. Asbestos bodies are golden brown, fusiform or beaded rods with a translucent center.
    2. It consists of asbestos fibers coated with an iron-containing proteinacous material.
    3. They arise when macrophages phagocytose asbestos fibers; the iron is presumable derived from phagocyte ferritin.
    4. Other inorganic particulates may become coated with similar iron-protein complexes and are called ferruginous bodies.
    5. Rare single asbestos bodies can be found in the lungs of normal people.
  2. Pleural plaques
    1. Pleural plaques are the well-circumscribed plaques of dense collagen that are often calcified.
    2. The develop most frequently on the anterior and posterolateral aspects of the parietal pleura and over the domes of the diaphragm.
Pathogenesis
graph TD 1["Asbestos"] 2["Serpentine chrysotile forms <br>- Less danger due to <br>- Accounts for 90% of the asbestos used in industry"] 3["Aerodynamic properties"] 4["More flexible, curled structure"] 5["Impacted in the upper respiratory passages"] 6["Removed by the mucocilliary elevator"] 7["Solubility"] 8["More soluble and thus leach from the tissue"] 9["Amphibole forms <br>- More danger"] 10["Straight, stiff structure"] 11["Align themselves in the airstream"] 12["Delivered deeper into the lungs"] 13["Penetrate epithelial cells"] 14["Reach the interstitium"] 15["Phagocytosed by macrophages"] 16["Activation of inflammasome"] 17["Release of proinflammatory factors and fibrogenic mediators"] 18["Interstitial inflammation and fibrosis"] 1 --> 2 2 --> 3 3 --> 4 4 --> 5 5 --> 6 2 --> 7 7 --> 8 1 --> 9 9 --> 10 10 --> 11 11 --> 12 12 --> 13 13 --> 14 14 --> 15 15 --> 16 16 --> 17 17 --> 18
Complications of Therapies
Granulomatous Diseases
Sarcoidosis
Hypersensitivity Pneumonitis
Pumonary Eosinophilia
Smoking-Related Interstitial Diseases
Desquamative Interstitial Pneumonia
Respiratory Bronchiolitis-Associated Interstitial Lung Disease
Pulmonary Langerhans Cell Histiocytes
Pulmonary Alveolar Proteinosis
Surfactant Dysfunction Disorders
DISEASES OF VASCULAR ORIGIN
Pulmonary Embolism and Infarction
Pulmonary Hypertension
Diffuse Pulmonary Hemorrhage Syndrome
Goodpasture Syndrome
Idiopathic Pulmonary Hemosiderosis
Polyangitis With Granulomatosis
PULMONARY INFECTIONS
Community-Acquired Bacterial Pneumonias
Streptococcus pneumoniae
Haemophilus influenzae
Moraxella catarrhalis
Staphylococcus aureus
Klebsiella pneumonia
Pseudomonas aeruginosa
Legionella pneumophila
Myocplasma pneumoniae
Community-Acquired Viral Pneumonia
Influenza infections
Human Metapneumovirus
Severe Acute Respiratory Syndrome
Health Care-Associated Pneumonia
Hospital-Acquired Pneumonia
Aspiration Pneumonia
Lung Abscess
Chronic Pneumonia
Histoplasmosis
Blastomycosis
Coccidioidomycosis
Pneumonia in the Immunocompromised Host
Pulmonary Disease in Human Immunodeficiency Virus Infection
LUNG TRANSPLANTATION
TUMORS
Fig. On the basis of histological criteria
Fig. On the basis of clinical criteria
Property
Squamous cell carcinoma
Adenocarcinoma
Small cell carcinoma
Large cell carcinoma
Epidemiology
  1. Highly associated with smoking
  2. Most common in indian sub-continent
  3. Most common among smokers
  4. Most common in male
  1. Not associated with smoking
  2. Most common in world
  3. Most common among non-smokers
  4. Most common in female
Highly associated with smoking
Etiopathogenesis (Genetic factors)
  1. Deletion in 3p, 9p and 17p chromosomes → Loss of tumor supperssor loci
  2. Mutation of TP53 gene → Overexpression of p53 protein
  3. Loss of expression of the Retinoblastoma (RB) tumor suppressor gene
  4. Inactivation of cyclin-dependent kinase inhibitor gene (CDKN2A) → Loss of its protein product (p16)
  5. Loss of Fibroblast growth factor receptor gene (FGFR1)
  1. Loss of function Mutation in EGFR, ALK, ROS, MET and RET gene
  2. Mutation in the KRAS gene
  1. Mutation in TP53 and RB gene
  2. Deletion of 3p chromosome
  3. Amplification of genes of MYC family
Prognosis and Response to treatment
Good prognosis
  1. Worst prognosis due to high metastasis
  2. But also highly responsive to Chemotherapy and Radiotherapy
Metastasis
  1. Highly metastatic
  2. Brain → Fist site for metastasis
  3. Adrenal → Second site for metastasis
Site of cancer
Central (Hilar region)
Peripheral region
Central (Hilar region)
Peripheral region
Morphology
Gross
graph TD 1["Squamous metaplasia/ Dysplasia"] 2["Carcinoma in situ<br>- Atypical cells may be identified in cytologic smears of sputum or in bronchial lavage fluids or brushings. <br>- Lesion is asymptomatic and undetectable on radiographs. <br>- Last for several years."] 3["Invasive squamous cell carcinoma"] 4["Grows exophytically into the bronchial lumen."] 5["Produces intraluminal mass."] 6["Obstruction of bronchus with further enlargement."] 7["Distal atelectasis and infection."] 8["Penetrate the wall of the bronchus."] 9["Infiltrate along the peribronchial tissue into the adjacent carina or mediastinum."] 10["Tumors grows along a broad front to produce a cauliflower-like parenchymal mass <br>that pushes lung substances ahead of it."] 1 --> 2 2 --> 3 3 --> 4 4 --> 5 5 --> 6 6 --> 7 3 --> 8 8 --> 9 3 --> 10
  1. Neoplastic tissue is gray-white and firm to hard.
  2. In bulky tumors, focal areas of hemorrhage or necrosis produces red or yellow-white mottling and softening.
  3. Sometimes, these necrotic foci cavitate.
Microscropic
Poorly differentiated
  1. Keratin pearl and keratinization are focal and not well developed.
  2. High mitotic activity.
Moderately differentiated forms
  1. Individual cell keratinization, intercellular bridges and keratin pearls are easily seen but not as extensive as well differentiated forms.
Well differentiated forms
  1. Presence of keratinization and intercellular bridges.
  2. Keratin pears are markedly eosinophilic.
Gross
Atypical adenomatous hyperplasia
  1. It is a small lesion (<=5 mm) characterized by dysplastic pneumocytes lining alveolar walls that are mildly fibrotic.
  2. It can be single or multiple and can be in the lung adjacent to invasive tumor or away from it.
Adenocarcinoma in situ
  1. It was formly called Bronchioalveolar carcinoma.
  2. It is a lesion less than 3 cm.
  3. It is composed entirely of dysplastic cells growing along preexisting alveolar septae.
  4. The cells have more dysplasia than atypical adenomatous hyperplasia.
  5. It may or may not have intracellular mucin.
Adenocarcinoma
  1. It is an invasive malignant epithelial tumor with glandular differentiation or mucin production by the tumor cells.
  2. It grow in various patterns, including acinar, lepidic, papillary, micropapillary, and solid with mucin formation.
    3. ● Microscopic:
    1. They vary histologically into following forms.
      1. Well-differentiated tumors with obvious glandular elements.
      2. Papillary lesions resembling other papillary carcinomas.
      3. Solid masses with only occasional mucin-producing glands and cells.
    2. Lepidic pattern of growth (Tumor cells crawl along normal-appearing alveolar septae.
  1. Cells features
    1. relatively small (generally smaller than 3 times the diameter of a small resting lymphocytes)
    2. scant cytoplasm
    3. ill-defined cell borders
    4. finely granular nuclear chromatin (Salt and pepper pattern), and
    5. absent or inconspicuous nucleoli.
    6. Round, oval, or spindle-shaped
    7. Prominent nuclear molding.
  2. High mitotic count.
  3. Cells grow in clusters that exihit neither glandular nor squamous organization.
  4. Necrosis is common and often extensive.
  5. Azzopardi effect: Basophilic staining of vascular walls due to encrustation by DNA from necrotic tumor cells.
Neuroendocarine markers
  1. Chromogranin
  2. Synaptophysin
  3. CD57
Paraneoplastic hormones
Carcinomas
Neuroendocrine Proliferations and Tumors
Miscellaneous Tumors
Metastatic Tumors
PLEURA
Pleural Effusion
Inflammatory Pleural Effusions
Non-inflammatory Pleural Effusions
Pneumothorax
Pleural Tumors
Solitary Fibrosis Tumor
Malignant Mesothelioma