Preface

Agam is a group of budding medicos, who are currently doing their under graduation in
various Medical Colleges across Tamil Nadu and Pondicherry. The group was initiated on 18th
November 2017, in the vision of uniting medicos for various social and professional causes.

We feel delighted to present you Agam Pathology notes prepared by Agam Divide and Rule
2020 Team to guide our fellow medicos to prepare for university examinations.

This is a reference work of 2017 batch medical students from various colleges. The team
took effort to refer many books and make them into simple notes. We are not the authors of the
following work. The images used in the documents are not copyrighted by us and is obtained from
various sources.

Dear readers, we request you to use this material as a reference note, or revision note, or
recall notes. Please do not learn the topics for the 1st time from this material, as this contain just the
required points, for revision.
Acknowledgement

On behalf of the team, Agam would like to thank all the doctors who taught us Pathology.
Agam would like to whole heartedly appreciate and thank everyone who contributed towards the
making of this material. A special thanks to Vignesh M, who took the responsibility of leading the
team. The following are the name list of the team who worked together, to bring out the material in
good form.

• Vidhya Lakshmi M D
• Shalika G
• Hannasha M Priyadharshini
• Vimal K
• Kretheka B
• Mahalakshmi K
• Manivasagam R
• Miruthubashini M
• Lavanya E
• Subhashree B
• Vijayalakshmi K
• Dhanshree Bakhru
• Amrutha Priya Devi B
• Yashwantha Elumalai Jagadeesan
• Vignesh. M
 THE LUNG
ESSAY:
1. Emphysema
2. Lobar pneumonia
3. Small cell CA of lung.
4. Bronchial Asthma
5. Bronchogenic CA.

SHORT NOTES:
1. Oat cell CA
2. Squamous cell CA
3. Mesothelioma
4. Basal cell CA of lung
5. Opportunistic lung infection in AIDS
6. Primary Atypical pneumonia
7. Carcinoid tumour of lung
8. Acute Respiratory Distress Syndrome
9. Bronchiectasis
10.Viral pneumonia
11.Pan-acinar emphysema
12.Good Pasture syndrome
13.Pneumoconiosis
14.Silicosis
15.Sarcoidosis
16.Asbestosis
17.Sarcoid granuloma
18.Hhypersensitivity pneumonitis
19.Cor pulmonale

SHORT ANSWERS:
1. Reid’s index
2. Byssinosis
3. Ferruginous bodies

UPDATES
PATHOLOGY AGAM
ESSAY
1. EMPHYSEMA
 Emphysema is characterized by irreversible enlargement of the airspaces distal to the
terminal bronchiole, accompanied by destruction of their walls without obvious fibrosis.
 Small airway fibrosis – present in patients with emphysema – contributes to airflow
obstruction.

CLASSIFICATION
Based on the segments of the respiratory unit involved, emphysema is classified into
four major types:
 Centriacinar (centrilobular) emphysema:
 Central or proximal parts of the acini, formed by respiratory bronchioles, are
affected; Inflammation around bronchi & bronchioles.
 Most common form of emphysema.
 Both emphysematous and normal airspace exist within the same acinus and lobule.
 Occurs predominantly in heavy smokers, often in association with COPD.
 Lesions are more common and more severe in the upper lobes, particularly the apical
segments.
 Panacinar (panlobular) emphysema:
 Acini are uniformly enlarged.
 Occurs more commonly in lower zones and anterior margins of the lung; most severe
at bases.
 Associated with α1-antitrypsin deficiency.
 Distal acinar (paraseptal) emphysema:
 Distal part of acinus is predominantly involved.
 Emphysema is more striking adjacent to the pleura, along the lobular connective
tissue septa and at the margins of lobules.
 Occurs adjacent to areas of fibrosis, scarring or atelectasis.
 More severe in the upper half of lungs.
 Underlies many cases of spontaneous pneumothorax in young adults.
 Airspace enlargement with fibrosis (irregular emphysema):
 Acinus is irregularly involved.
 Mostly associated with scarring.
 Mostly occurs in small foci and is clinically insignificant.

AGAM PATHOLOGY
PATHOGENESIS
Smoking / Air Pollutant + Genetic Predisposition

Resident epithelial cells and macrophages release Leukotriene B4, IL-8, TNF

Attract inflammatory Release several proteases

cells

Oxidative stress Inflammation amplified Relative deficiency of

antiprotease

Alveolar wall Protease- antiprotease

destruction imbalance

 Patients with congenital α1-antitrypsin deficiency have a ↑ tendency to develop

pulmonary emphysema (due to protease-antiprotease imbalance
 Certain variants of the nicotine acetylcholine receptor are hypothesized to influence the
addictiveness of tobacco smoke and thus, the behaviour of smokers resulting in an
enhanced risk of developing emphysema.
 Airway Obstruction In Emphysema
Loss of elastic tissue in the walls of alveoli surrounding respiratory bronchioles

Reduced radial traction

Respiratory bronchioles collapse during expiration

Functional airflow obstruction

 In addition, even young smokers often have small airway inflammation associated with:
 Goblet cell hyperplasia, with mucus plugging of the lumen.
 Inflammatory infiltrates in bronchial walls consisting of neutrophils, macrophages, B
cells and T cells.
 Thickening of the bronchial wall due to smooth muscle hypertrophy and
peribronchial fibrosis.

PATHOLOGY AGAM
MORPHOLOGY
 Gross Features
 Voluminous lungs, often overlapping the heart and hiding it.
 Upper 2/3rds of lungs are more severely affected.
 Large apical blebs or bullae (in irregular emphysema or distal acinar emphysema).
 Histology
 Abnormally large alveoli separated by thin septa with only focal centriacinar fibrosis.
 Large pores of Kohn.
 Decrease in the capillary bed area (due to destruction of alveolar walls).
 Prolonged vasoconstriction → Pulmonary arterial hypertension.

CLINICAL COURSE
 Asymptomatic until at least 1/3rd of the functioning pulmonary parenchyma is
damaged.
 Chief complaints: Dyspnoea (insidious in onset, progressive), cough or wheezing.
 Weight loss is common.
 Classic features of severe emphysema: Patient is;
 Patients may over ventilate and remain well-oxygenated. Hence, called pink puffers.
 Sits in hunched-over position.  Barrel-chested.
 Breathes through pursed lips.  Dyspnoeic.
 Impaired expiratory flow.  Severe overdistension.
 Cough, if present, is slight.  Low diffusion capacity.
 Development of cor pulmonale and CCF – poor prognosis.
 Death is due to:
 Massive collapse of lungs 2o to pneumothorax  Respiratory Failure
 Coronary artery disease  Right Heart Failure

TREATMENT
 Lung volume reduction surgery and lung transplantation (selected patients).
 Long-acting bronchodilators with inhaled steroids
 Smoking cessation  Physical therapy
 Oxygen therapy  Bullectomy

OTHER FORMS OF EMPHYSEMA

 Compensatory hyperinflation  Bullous Emphysema
 Obstructive over-inflation  Interstitial Emphysema

AGAM PATHOLOGY
2. LOBAR PNEUMONIA
 Lobar pneumonia involves consolidation of a large portion of a lobe or of an entire lobe.

CAUSES OF LOBAR PNEUMONIA

Depending on bacterial virulence and host resistance, the same organism can cause
bronchopneumonia or lobar pneumonia.
 Streptococcus pneumoniae
 Most common cause of community-acquired pneumonia.
 Diagnosis: Presence of numerous neutrophils containing the typical gram-positive,
lancet-shaped diplococci in Gram-stained sputum.
 Pneumococcal vaccines are used in individuals at high risk for pneumococcal sepsis.
 Haemophilus influenzae
 Pleomorphic, gram-negative organism; encapsulated and non-encapsulated.
 Six serotypes of encapsulated form – type b most virulent.
 Routine use of H. influenzae conjugate vaccines → Rreduced incidence of disease
caused by type b.
 Infections with non-encapsulated forms, also called non-typeable forms, are on the
rise; Patients present with otitis media, sinusitis and bronchopneumonia.
 H. influenzae pneumonia, following a viral respiratory infection, is a pediatric
emergency.
 Pulmonary consolidation: Usually lobular and patchy, but maybe confluent and
involve the entire lung lobe.
 H. influenzae is the most common bacterial cause of acute exacerbation of COPD.
 Moraxella catarrhalis
 Affects the elderly more.
 2nd most common bacterial cause of acute exacerbation of COPD.
 Klebsiella pneumoniae
 Most frequent cause of gram-negative bacterial pneumonia.
 Commonly affects debilitated and malnourished people and chronic alcoholics.
 Thick, mucoid, (often blood-tinged) sputum.
 Legionella pneumophilia
 Causes Legionnaires’ disease and Pontiac fever.
 Common in individuals with cardiac, renal, immunologic, or hematologic disease.
 Organ transplant patients are particularly susceptible.

PATHOLOGY AGAM
MORPHOLOGY
 Four stages of the inflammatory response have classically been described:
 Congestion (<24 hours)
 Lung is heavy, boggy and red.
 Characterized by vascular engorgement, intra-alveolar fluid with few neutrophils,
and presence of numerous bacteria.
 Red hepatization (2-3 days)
 Lobe is red, firm, and airless with a liver-like consistency.
 Cut section: Red granular
 Characterized by massive confluent exudation, as neutrophils, red cells and fibrin fill
the alveolar spaces.
 Gray hepatization (5-7 days)
 Greyish-brown coloured
 Cut section: Grey, dry granular
 Progressive disintegration of red cells
 Presence of a fibrinosuppurative
 Resolution
 Affected lobe become crepitated
 Neutrophils  Fibrinolytic enzymes  Liquefaction of exudates  Granular material
and semifluid debris  Resorbed  Ingested by macrophages → Expectorated, or
organised by fibroblast growing into it.
 Pleural fibrinous reaction to the underlying inflammation may resolve.
 More often, there is fibrous thickening or permanent adhesion.

CLINICAL COURSE
 Major symptoms:
 Abrupt onset of high fever,
 shaking chills,
 Cough producing mucopurulent sputum and occasionally haemoptysis.
 Pleuritic pain and pleural rub (when pleuritis is present).
 Whole lobe is radiopaque in lobar pneumonia.

AGAM PATHOLOGY
3. SMALL CELL CARCINOMA:
 Originate from Neuroendocrine Tumors
 Highly Malignant
 Frequently located at Hilar or Central in Origin
 Reson is due to Ectopic Hormone Production

MORPHOLOGY:
 Small cell lung cancer (SCLC) consists of small cells with a high nucleo-cytoplasmic ratio
that proliferate rapidly.
 Similar to normal neuroendocrine cells, they contain neurosecretory granules that may
produce peptide hormones and/or biogenic amines.
 About 90% of small cell lung cancers stain positive for neuroendocrine markers.
 Small cell lung cancers usually develop peribronchially and infiltrate the bronchial
submucosa.
 This tumor type can be diagnosed in cytological material such as fine needle aspirations,
brush specimens, or lavage.
 The diagnosis should, if possible, be confirmed in histological specimens before starting
therapy.
 Pure small cell carcinoma:
 small-car like,uniform but larger than lymphocytes
 Nucleus having diffuse chromatin
 Cells are Organised into Cords,Aggregates and Ribbons.
 Combined small cell carcinoma
 Small cell carcinoma combined with Non-small cell carcinoma.

ETIOLOGY:
 Peak incidence in 55 to 65 years
 The main Etiology of Bronchogenic Carcinoma is cigarrete smoking.
 80% of lung cancer are primarily due to cancer.
 Histological alteration: The association of tobacco smoking for squamous cell carcinoma.
 Mechanism: The Tar from Ciggarette smoking has known to contain a number of
Carcinogens
 Radiation exposure  Chronic Scarring
 Atmospheric pollution  Diet
 Occupational causes

PATHOLOGY AGAM
PATHOGENESIS:
 Activation of Growth Producing Oncogenes:
 Mutation in K-RAS oncogene-commonly
 Mutation in EGFR oncogene-Adenocarcinoma in non smokers
 Others-BRAF,PIK3CA,MYC Family
 Inactivation of Tumor Suppressor gene:
 Many tumor suppressor gene is found in Chromosome 3p
 Inactivation of p53 and Rb gene
 Autocrine growth factors:
 Nicotine acts as initiator as well as promote of carcinogens
 Inherited Predispostion:
 Some people have inherited P53 mutation Eg: Li Fraumeni syndrome
 Molecular targets for therapy and survival
 EGFR Mutation
 ALK rearrangement
 VEGF and monoclonal therapy.

SPREAD BY
 Directly,by invading wall of the Bronchus
 Lymphatic spread, bipolar lymph nodes spread through Mediastinal, cervical,
supraclavicular and para aortic.
 Hematogenous via blood stream.

CLINICAL FEATURES
 Cough,  Other obstructive symptoms include,
 Chest pain,  Bronchopneumonia,
 Dyspnea,  Lung abcess,
 Haemoptysis  Bronchiectasis.
 Symptoms of Metastasis include superior vena cavalry syndrome,painful body
lesions, paralysis of recurrent laryngeal nerve.

STAGING
 Stage 1: Tumor less than 3cm
 Stage 2: Tumor larger than 3cm
 Stage 3: Any size with hilar lymphnodes.

AGAM PATHOLOGY
4. BRONCHIAL ASTHMA
Asthma is a chronic disorder of the conducting airways, usually caused by an
immunological reaction, which is marked by episodic bronchoconstriction due to increased
airway sensitivity to a variety of stimuli; inflammation of the bronchial walls; and increased
mucus secretion.
TYPES:
 Atopic asthma:
 Most Common type of Asthma,
 Ther is evidence of allergen sensitization and immune activation, often in patient
with allergic rhinitis or eczema
 IgE mediated Type I hypersensitivity
 Begins in childhood, (+ve) Family history present
 Triggered by environmental allergens (Dusts,Pollen,Cockroach,Animal Dander,Food)
 Skin test: Immediate Wheel & Flare reaction
 Non-atopic asthma:
 No Evidence of Allergen Sensitization
 Skin test: (-ve), Family history (-ve)
 Triggered by Viruses (Rhinovirus, Parainfluenza, Respiratory Syncytial Virus), Inhaled
Air pollutants (Smoking, Sulfur dioxide, ozone, NO)
 Attacks may be triggered by innocuous events such as exposure to Cold & Exercise
 Drug induced asthma:
 It is a Uncommon Type, with no evidence of Allergen sensitization
 Pharmacological agents such as ASPIRIN & NSAIDs provoke asthma sometimes
 These individuals experience not only Asthma but also Utricaria.
 Aspirin & NSAIDs triggers Asthma by inhibiting COX pathway leading to ↓ PGE2
 Normally PGE2 inhibits enzymes that generate pro inflammatory mediators that
believed to have central role in this type of asthma.
 Occupational asthma:
 Triggered by
 Fumes (Epoxy resins, Plastics)
 Organic & Chemical Dusts (Wood, Cotton, Platinum)
 Gases (Toluene)
 Other Chemicals (Formaldehyde, Penicillin products)
 Only minute quantities of chemicals required to induce the attack, which usually
occurs after repeated exposure.

PATHOLOGY AGAM
PATHOGENESIS:
 Atopic Asthma is caused by a TH2 & IgE response to Environmental allergens in
genetically pre-disposed individuals.
 Airway inflammation is central to disease pathophysiology & causes airway dysfunction
partly through the release of potent inflammatory mediators & partly through
remodelling of airway wall.
 Contributing Factors:
 TH2 Responses, IgE and Inflammation
 Genetic Susceptibility
 Environmental Factors

Th2 responses, IgE & inflammation

 A fundamental abnormality in asthma is an exaggerated TH2 response to normal
harmless environmental antigen.
IL-4 → ↑Production of IgE
 TH2 secretes IL-5 → Activates locally recruited Eosinophils
IL-13 → ↑Mucus Secretion, IgE (by B cells)
 T cells & Epithelial cells secrete chemokines that recruit more T cells and eosinophils,
thus exacerbating the reaction.

IgE binds with Fc receptors on submucosal mast

cells

Mast cell Degranulation

Release of cytokines & other mediators

Early Phase reaction Late Phase reaction

 Bronchoconstriction Recruitment of leukocytes,
 ↑ Mucous secretion notably eosinophils,
 Vasodilation neutrophils, and more T cells
 ↑ Vascular Permeability

AGAM PATHOLOGY
 Many mediators produced by leukocytes and epithelial cells have been implicated in the
asthmatic response.
 Leukotriene C4, D4, E4: cause prolonged bronchoconstriction, increased vascular
permeability and increased mucus secretion
 Acetylcholine: released from intrapulmonary parasympathetic nerves, which can
cause airway smooth muscle constriction by directly stimulating muscarinic receptors
 Histamine: a potent bronchoconstrictor
 Prostaglandin D2: elicits bronchoconstriction & vasodilatation
 Platelet-activating factor: causes aggregation of platelets
 Others: IL-1, TNF, IL-6, chemokines, neuropeptides, nitric oxide, bradykinin, and
endothelins.

Genetic susceptibility:
 Susceptibility to Atopic Asthma is multigenic and often associated with increased
incidence of other allergic disorders, such as allergic rhinitis (hay fever) and eczema
 One susceptibility locus for Asthma is located on Chromosome 5q(IL-13 gene)
 Particular class II HLA alleles are linked to production of IgE antibodies against some
antigens, such as ragweed pollen.
 Polymorphisms in the gene encoding ADAM33
 IL-4 receptor gene variants are associated with atopy, elevated total serum IgE, and
asthma
 Increased serum levels and lung expression of YKL-40

Environmental factors:
 Asthma is a disease of industrialized societies where the majority of people live in cities
 This likely has 2 main explanations
 Hygiene hypothesis
 Industrialized environments contain many airborne pollutants that can serve as
allergens to initiate the TH2 response

PATHOLOGY AGAM
MORPHOLOGY:
 Gross, in patient dying of Acute Severe Asthma
 Lungs are distended by over-inflation
 Contains small areas of Atelectasis
 Occulusion of Bronchi & Bronchioles by thick, tenacious mucus plugs, which contains
shed epithelium.
 Microscopically,
 Curschmann spirals
 These are degenerated respiratory epithelium forming twisted strips seen in sputum
& Broncho-Alveolar Lavage specimen.
 Charcot-Leyden crystals
 The sputum contains numerous eosinophils & diamond shaped crystals composed of
eosinophil proteins called galectin-10.
 Airway Remodeling,
 Thickening of Airway wall
 Subbasement Membrane fibrosis
 Increased vascularity
 Increase in size & Number of sub mucosal glands
 Hypertrophy & or hyperplasia of Bronchial wall muscle
CLINICAL COURSE:
 A classic acute asthmatic attack lasts up to several hours
 Cardinal Symptoms;
 Chest tightness
 Dyspnea
 Wheezing
 Coughing (with or without sputum production)
 Rarely, a state of unremitting attacks, called ACUTE SEVERE ASTHMA (Previously known
as STATUS ASTHMATICUS) may prove fatal: usually such patient may have had a long
history of asthma between the attacks, patient may be virtually asymptomatic.
DIAGNOSIS:
 Demonstration of an increase in airflow obstruction (from baseline levels)
 Difficulty with exhalation (prolonged expiration, wheeze)
 Peripheral blood eosinophilia
 Curschmann spirals & Charcot-Leyden crystals in the sputum (particularly in patients
with atopic asthma).
AGAM PATHOLOGY
5. BRONCHOGENIC CARCINOMA
 Lung cancer is currently the most frequently diagnosed major cancer in the world.
 It is the most common cause of cancer mortality worldwide
 This is largely due to carcinogenic effects of cigarette smoke
 Cancer of Lung occurs most often between ages 40-70 years, with a peak incidence in
50s or 60s.
 Only 2% of all cases appear before the age of 40.

ETIOLOGY
 Tobacco Smoking  Air Pollution
 Industrial Hazards  Genetic Causes

PATHOGENESIS:
 Tobacco smoking
 About 80% of lung cancers occur in Active smokers those who stopped recently.
 There is nearly linear correlation between frequency of Lung cancer & pack years of
cigarette smoking
 The increased risk becomes 60 times greater among habitual heavy smokers
(2packs/day for 20 years) compared with non-smoker
 However, since lung cancer develops in only 11% of heavy smokers, there are other
factors that pre-dispose individuals to this deadly disease
 Women are more susceptible to carcinogen in tobacco than Men
 Although, Cessation of smoking decreases the risk for Lung cancer over time, it may
never return to baseline levels.
 Genetic changes that predate lung cancer can persist for many years in the bronchial
epithelium of former smokers
 Passive smoking increases the risk for lung cancer development to approximately
twice that of non-smokers
 Although the duration and intensity of smoking are well correlated with cancer risk,
not all persons exposed to tobacco smoke develop cancer
 Some of this may be a matter of chance, but it is also likely that the mutagenic effect
of carcinogens in smoke is modified by genetic variants.
 Specific P-450 polymorphisms have an increased capacity to activate pro carcinogens
in cigarette smoke, and smokers with these genetic variants appear to incur a greater
risk of lung cancer.

PATHOLOGY AGAM
 Industrial hazards
 Chemical exposures such as asbestos, arsenic, Chromium, Uranium, Nickel, Vinyl
chloride increase the risk of lung cancer
 There was an increased incidence of lung cancer among survivors of the Hiroshima
and Nagasaki atomic bomb blasts, as well as in workers heavily involved in clean-up
after the Chernobyl disaster
 Cancer rates among non-smoking Uranium miners are 4 times higher than those in
general population, among smoking miners they are about 10 times higher.
 Lung cancer is the most frequent malignancy in individuals exposed to asbestos

 Air pollution
 Air pollution may itself increase the risk of lung cancer or adds to the risk in those
who smoke/ passive smokers.
 Chronic exposure to air particles in smog → Lung irritation → Inflammation → Repair
→ ↑ Risk of cancer
 A specific form of air pollution that may contribute to an increased risk of lung cancer
is Radon gas.
 Radon is a ubiquitous radioactive gas that has been linked epidemiologically to
increased lung cancer in uranium miners, particularly those who smoke

 Lung cancer in never smokers

 The WHO estimates that 25% of lung cancer worldwide occurs in never smokers.
 These cancers occur more commonly in women and most are adenocarcinomas.
 Cancers in non-smokers are more likely to have EGFR mutations, and almost never
have KRAS mutations
 TP53 mutations are also seen.

PRECURSOR / PREINVASIVE LESIONS:

 The term precursor does not imply that progression to cancer is inevitable.
 Currently it is not possible to distinguish between precursor lesions that progress and
those that remain localized or regress
 4 types of morphologic precursor epithelial lesions are recognized:
 Squamous dysplasia and carcinoma in situ
 Atypical adenomatous hyperplasia
 Adenocarcinoma in situ
 Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia.

AGAM PATHOLOGY
TUMOR CLASSIFICATION:

 Squamous cell carcinoma

 Papillary carcinoma
 clear cell carcinoma
 small cell carcinoma
 basaloid carcinoma
 Small-cell carcinoma
 Combined small-cell carcinoma
 Adenocarcinoma
 Minimally invasive adenocarcinoma (non-mucinous, mucinous)
 Lepidic
 Acinar
 papillary, solid (according to predominant pattern)
 Mucinous adenocarcinoma
 Large cell carcinoma
 Large-cell neuroendocrine carcinoma
 Adenosquamous carcinoma
 Carcinomas with pleomorphic, sarcomatoid, or sarcomatous element
 Carcinoid tumor
 Typical, atypical
 Carcinomas of salivary gland type

 For therapeutic purposes, bronchogenic carcinoma can be classified into 3 groups:

 Small cell carcinomas, SCC
 Non-small cell carcinomas, NSCC (includes squamous cell carcinoma,
adenocarcinoma, and large cell carcinoma)
 Combined/mixed patterns

PATHOLOGY AGAM
 Small Cell Carcinoma (14%)
 Location: Central
 Genetic Factors: Loss of function abberations involving TP53, RB, Chromosome 3p
deletion
 Histology: Poorly differentitated small cells, arises from Neuroendocrine (kulchitsky)
cells, chromogranin positive
 Rapid growth & Early metastasis
 May produce endrocrine (ADH/ ACTH) or Nervous system (Lambert-eaton
myasthenic syndromes)
 Associated with Male smokers
 Squamous Cell Carcinoma (20%)
 Location: Central
 Genetic Factors: Chromosome deletions involving tumor suppressor loci especially
those involving 3p, 9p, 17p, RB,CDKN2A
 Histology: Keratin Pearls or intercellular bridges
 May produce PTHrP
 Most common tumor in male smokers
 Adenocarcinoma (38%)
 Location: Peripheral
 Genetic Factors: Gain of function mutation - EGFR, ALK, ROS, MET, RET
 Histology: Glands or mucin
 Adenocarcinoma in-situ exhibits columnar cells that grow along preexisting
bronchioles and alveoli
 May present as pneumonia like consolidation on imaging
 Most common tumor in Non-smokers & Female smokers
 Large Cell Carcinoma (3%)
 Location: Central or peripheral
 Histology: Poorly differentiated large cells (no keratin pearls, intercellular bridges,
glands, or mucin)
 Poor prognosis
 Immunohistochemistry for TTF-I (adeno), p40 (squamous) or chromogranin
(neuroendocrine) may allow for more specific classification
 Associated with smoking

AGAM PATHOLOGY
 Bronchial Carcinoid Tumour:
 Location: Central or peripheral: when central forms a polyp like mass in the bronchus
 Histology: Well differentiated neuroendocrine cells (nests); chromogranin positive
 Low grade malignancy
 Rarely, can cause carcinoid syndrome

TNM STAGING:
 T – TUMOR SIZE & LOCAL EXTENSION - (T0 – T4)
 N – SPREAD TO REGIONAL LYMPH NODES - (N0 – N3)
 M – METASTASIS - (M0 – M1)

CLINICAL COURSE:
 Lung cancer is one of the most insidious and aggressive neoplasms in the realm of
oncology.
 The major presenting complaints are
 Cough (75%)
 Weight loss (40%)
 Chest pain (40%)
 Dyspnea (20%).
 Symptoms of metastases depend on the site, for example, back pain in bone
metastases, headache, hemiparesis, cranial nerve damage, and seizures in brain
metastases.
 In general, adenocarcinoma and squamous cell carcinoma tend to remain localized
longer and have a slightly better prognosis than do the undifferentiated cancers, which
are usually advanced by the time they are discovered.
 Apical lung cancers in the superior pulmonary sulcus tend to invade the neural
structures around the trachea, including the cervical sympathetic plexus, and produce a
group of clinical findings that includes severe pain in the distribution of the ulnar nerve
and Horner syndrome (enophthalmos, ptosis, miosis, and anhidrosis) on the same side
as the lesion. Such tumors are also referred to as PANCOAST TUMORS.
 Lung cancers, particularly small cell lung carcinomas, can cause PARANEOPLASTIC
SYNDROMES.

PATHOLOGY AGAM
SHORT NOTES
1. SMALL CELL CARCINOMA (OAT CELL CARCINOMA)
 Most malignant lung carcinoma  Wide metastasis
 Most aggressive  Fatal
 Location: Central
 Etiology & risk factors:
 Scars: Granulomatous, fibrosis, scleroderma.  Radiation exposure
 Cigarette smoking  Genetic factors
 Asbestos Inhalation  Air pollution
 Spread:
 Limited stage: Involvement of lung and single lymph node
 Extended stage: wide spread
 Molecular genetics:
 Frequent loss of function mutation of TP53, RB, chromosome 3p deletion,
p16/CDKN2A Mutation.
Rare KRAS Mutation
Amplification of genes of the MYC family.
 GROSS FEATURES: Pale grey, centrally located masses that extend into lung
parenchyma.
 Light microscopy:
 OAT CELLS with salt and pepper pattern
 Nuclear molding is prominent with scant cytoplasm.
 Numerous mitotic figures are present.
 Tumor cells are fragile and often show fragmentation and crush artefact in small
biopsy specimens.
 Basophilic staining of vascular walls due to encrustation by DNA from necrotic tumor
cells (AZZOPARDI EFFECT)
 Electron microscopy: Dense core neuroscretory granules releasing neuroendocrine
markers such as chromogranin, synaptophysin, and CD57, parathormone-related
protein.
 Most common lung Ca associated with ectopic hormone production like ACTH, ADH,
GRP, calcitonin.
 Epithelial markers – epithelial membrane antigen, carcinoembryonic antigen and
cytokeratin intermediate filaments present.

AGAM PATHOLOGY
 Immunohistochemistry: BCL2 in 90% of tumors
 Clinical features:
 Pulmonary features:
 Cough  Hemoptysis
 Dyspnea, Hoarseness  Chest pain
 Superior vena cava syndrome:
o 1.facial edema,
o 2.prominent veins in chest
 Paraneoplastic features:
 Release of ADH, SIADH, ACTH, CORTISOL.
 Clubbing of the fingers and hypertrophic pulmonary osteoarthropathy.
 Lambert-Eaton Myasthenic Syndrome-++
 Metastatsis: Involving lung, adrenal gland, CNS
 Diagnosis: X-Ray, PET Scan.
 Treatment: Response to chemotherapy and radiotherapy often complete but recur
invariably

2. SQUAMOUS CELL CARCINOMA:

 A rare type of Non-small cell lung Carcinoma
 Common among Men with the History of Tobacco Smoking
 Arises from: Large Bronchus and then joins the trachea.
 Spread of Small Cell Carcinoma is rapid
MORPHOLOGY:
 Arises from epidermis, Has intracellular bridges and keratinisation
 Squamous cell carcinoma is often a centrally located tumor close to the hilum.
 Histologic hallmarks of squamous cell carcinoma are polygonal cells with intercellular
bridges, crisp eosinophilic cytoplasm.
 Tumors may also contain keratin pearls, and larger tumors may have extensive necrosis.
STAGES
 Stage 1: the cancer is localized and has not spread to any lymph nodes
 Stage 2: the cancer has spread to lymph nodes or the lining of the lungs, or is in a
certain area of the main bronchus
 Stage 3: the cancer has spread to tissue near the lungs
 Stage 4: the cancer has spread (metastasized) to another part of the body, the most
common sites being the bones, brain, liver, or adrenal glands
PATHOLOGY AGAM
3. MESOTHELIOMA
 Mesotheliomas can be pleural or peritoneal or pericardial
and are associated with asbestos exposure
 In contrast to lung cancers, these tumors do not appear to
be associated with smoking
 Epidemiology:
 Rare tumor but risk of mesothelioma in heavily asbestos exposed individuals(25-45
yrs)
 SV40(simian virus40) is often associated
 Molecular genetics:
 Homozygous deletion of the tumor suppressor gene CDKN2/INK4a.
 Mutations in pathways involved in DNA repair, cell cycle control and growth factor
signaling.
 Commonly mutated genes in sporadic mesothelioma - BAP1 – encodes a tumor
suppressor involved in DNA repair that also is affected by germline mutations.
 Gross morphology:
 DIFFUSE LESION arising either from visceral or parietal pleura
 May cause extensive pleural effusion and direct invasion of thoracic structures.
 Often preceded by extensive pleural fibrosis and plaque formation.
 At autopsy – long typically is ensheathed by a layer of yellow white, firm, variably
gelatinous tumor.
 Light microscopy:
 Epithelioid (60%) – m.c. variety
 Sarcomatoid (20%)
 Mixed (20%)
 IHC: strong positivity for keratin proteins,calretinin,WT-1,cytokeratin 5/6and D2-40
 Electron microscopy: Long microvilli and abundant tonofilament but absent microvillus
rootlets and lamellar bodies.
 Clinical features: chest pain, dyspnea, recurrent pleural effusion
 Differential diagnosis: Pulmonary adenocarcinoma
 Diagnosis: Cytological examination of pleural fluid, biopsy of pleural tissue.
 No effective therapy

AGAM PATHOLOGY
4. BASAL CELL CARCINOMA OF LUNG:
 Although basal cell carcinoma is the most common skin cancer, it rarely metastasizes.
 Metastatic basal cell carcinoma may, therefore, initially elude diagnosis and
management.
 The male-female ratio of the incidence of BCC metastasis is 2:1
 MBCC is most often manifested as a dissemination to the regional lymph nodes (60%) or
hematogenous spread to the lung (42%), bone (20%), or skin (10%), with symptoms such
as lymphadenopathy, ulceration, anemia, bone pain, and muscle weakness depending
on the site of metastasis.
 The lung, although a distant site, is most often involved in MBCC, and almost 50 such
cases have been reported to date.
 Most MBCCs involving the lungs are disseminated multiple small nodules that originate
because of hematogenous spread.

5. PULMONARY DISEASE IN HIV INFECTION

 HIV affected individuals  Immunocompromised  Opportunistic Infections 
Pneumonias  High mortality
 Infectious pulmonary infiltrates in HIV infected individuals:
 Bacteria – more common, severe, a/w bacteraemia (S. pneumonia, S. Aureus, H,
influenza, gram negative)
 Virus (CMV, herpes)
 Fungi (pneumocystis’ jiroveci, aspergillus, candida
 Non-infectious pulmonary infiltrates in HIV infected individuals:
 Kaposi sarcoma
 Lung cancer
 Pulmonary Non-Hodgkin lymphoma
 CD4+ T cel count – to determine risk of infection:
 Bacterial and TB infections- >200cells/mm3
 Pneumocystitis pneumonia- <200cells/mm3
 CMV, Mycobacterium avium, fungal- <50cells/mm3

PATHOLOGY AGAM
6. ATYPICAL PNEUMONIA
 Nonbacterial etiology
 Interstitial tissue inflammation and Mononuclear cell infiltration
CAUSATIVE ORGANISMS:
Atypical organismsnot detectable on gram staining/do not grow on standard
bacteriologic culture media
 Influenza virus type a
 Has 8 ss-DNA
 2 proteins responsible for virulence – hemagglutinin and neuraminidase
 Hemagglutininattach virus to target celluptake into endosomesacidification of
endosomefusion of viral envelope with the cell membranerelease of viral RNA
 Neuraminidasecleaves salicylic acid residuesrelease of new virions
 Ag drift and Ag shift in these proteins are responsible for epidemics and pandemics
resp.
 Pathogenesis:
Virus  pneumocytes  Na+channels inhibited  Fluid accumulation in
alveoli resulting in:
 Activation of caspases  Pneumocyte apoptosis
 Danger signals  Macrophage activation  Pulmonary endothelial
activationARDS
 Secondary bacterial infection  Staph aureus  Fatal
 Control of infection:
 Innate immunity  alpha and beta interferon  interferes with viral
replication
 Nk cells, cytotoxic T cellskills infected host cells
 Ab against neuraminidase and hemagglutinin
 Aspirin – contraindicated – causes Reye Syndrome
 Mycoplasma pneumoniae
 Most common cause
 a/w formation of Ig M Abcold autoimmune haemolytic anemia
 Occur Sporadically or as local epidemics in closed communities
 Diagnosis – PCR and Antigen detection.
 Chlamydophilia pneumoniae  Pneumocystitis jiroveci
 2nd most common  Fungal infection in HIV patients
 High risk of CAD  Silver staining

AGAM PATHOLOGY
 Human metapneumovirus
 Any age grp, immunocompromised
 a/w upper and lower respiratory tract infection
 causes bronchiolitis and pneumonia
 diagnosis: PCR, direct immunofluorescence
 treatment: ribavirin
CLINICAL FEATURES:
 Low grade fever  Dry cough
 No signs of consolidation  Malaise/myalgia
INVESTIGATION: Sputum  staining negative, Chest x ray

7. CARCINOID TUMORS OF LUNGS

 Carcinoid tumors are malignant tumors composed of cells that contain dense-core
neurosecretory granules in their cytoplasm and rarely may secrete hormonally active
polypeptides.
 Epidemiology:
 1%-5% of all lung tumors
 Age of onset:< 40 yrs
 20-40% -non smoker
 Classification:
 Classical carcinoid: lack necrosis
 Atypical carcinoid: Pleomorphism, necrosis, prominent nucleoli, may cause
carcinoid syndrome
 Clinical features:
 Obstructive line bronchiectasis, emphysema, atelectasis. Cough, hemoptysis,
recurrent bronchial and pulmonary infections.
 carcinoid syndrome-diarrhea, flushing, cyanosis
 Gross Central/peripheral, some tumors penetrate bronchial wall, collar button lesion,
and spherical polypoidy masses projecting into lumen seen in few cases.
 Microscopy: Typical carcinoids - Nest/rosette-like arrangement of cells separated by
delicate fibrovascular stroma with salt and pepper chromatin.
 Atypical carcinoids – high mitotic rate and small foci of necrosis.
 IHC: Stains positive for serotonin, Neuron-specific enolase, Bombesin, Calcitonin

PATHOLOGY AGAM
8. ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)
 Also called as Shock lung / Stiff lung / Hyaline membrane disease / Non cardiogenic
pulmonary edema
 Lung injury  within 7 days  acute respiratory failure
 Bilateral pulmonary opacities
 Not explained on the basis of pre-existing cardiac problem / volume overload / pleural
effusion/atelectasis
ETIOLOGICAL FACTORS:
 Direct factors
 Diffuse pulmonary infections  Gastric aspiration
 Inhaled irritants (oxygen toxicity, smoke)
 Indirect injury
 Mechanical trauma( including head injury)  Sepsis
 Haematological conditions  Pancreatitis
 Transfusion associated lung injury  Drugs
 Disseminated intravascular coagulation  Burns
PATHOGENESIS: 
Endothelial Injury

IL-8 (strongly chemotactic) Increased permeability

Sequestration of neutrophils into alveoli Exudative Fluid

Release of Oxygen derived free radicals, Pinkish alveolar membrane (due to

protease, and leukotriene deposition of fibrin / necrotic cells)

Alveolar epithelial cell injury Hyaline Membrane Disease

↓ Surfactants and ↑ Surface tension ↓ Compliance

Alveolar collapse Stiff Lung

Diffuse Alveolar Damage

AGAM PATHOLOGY
 Radiological finding: Diffuse bilateral infiltrates
 Morphology:
 Lungs are dark red, firm, airless and heavy.
 Microscopic – capillary congestion and necrosis of alveolar epithelial cells, interstitial
and intra alveolar edema and haemorrhage, collection of neutrophils in capillaries.
 Hyaline membranes.
 Organising stage – type II pneumocytes proliferate - attempt to regenerate the
alveolar lining.
 Marked thickening of the alveolar septa ensues due to proliferation of interstitial
cells and deposition of collagen.
 Clinical features:
 Dyspnoea and tachypnea  Respiratory failure
 Cyanosis and hypoxemia  Ventilation perfusion mismatch

9. BRONCHIECTASIS
 Destruction of smooth muscle and elastic tissue by chronic nectrotizing infection leads
to permanent dilatation of bronchioles and bronchi.
 Causes:
 Herediatary conditions – Cystic fibrosis, Kartagener syndrome, immunodeficiency
States, primary ciliary dyskinesia.
 Infections – Necrotizing or suppurative pneumonia
 Bronchial obstruction – Tumour & Foreign bodies and impaction of mucus.
 Idiopathic.
 Pathogenesis:
 Obstruction → Clearance mech. impaired → Pooling of secretion → Inflammation →
Infection of Bronchi → Inflammation → Necrosis & Fibrosis → Bronchial dilation
 Cystic Fibrosis: Defect in ion transport → Defective muco-cilliary action →
Obstruction of airway by thick mucous secretion.
 Primary ciliary dyskinesia: Dynein protein defect → Retention of secretion →
Recurrent infection → Bronchiectasis.
 Allergic pulmonary aspergillosis: Hypersensitivity → Airway inflammation with
eosinophils → Formation of mucous plugs.

PATHOLOGY AGAM
 Morphology :
 Affect lower lobe Bilaterally and vertical passages.
 Most severe involvement found in the more distal bronchi and bronchioles.
 Airways are dilated four times their usual diameter.
 Bronchi appear Cystic and filled with mucopurulent secretions.
 Full blown case – Acute and Chronic inflammation, Desquamation of lining
epithelium, Areas of ulceration in walls of Bronchi.
 Mixed flora is cultured from the sputum
 Pseudostratification of Columnar/Squamous metaplasia and Fibrosis.
 Abnormal dilation and scarring may persist.
 Necrosis destroys the bronchial or bronchiolar walls producing an abscess cavity.

 Complications:
 Cor pulmunale
 Brain abcesses
 Amyloidosis.

 Clinical features:
 Severe persistent cough
 Expectoration of foul-smelling sputum
 Dyspmoea
 Orthopnoea
 Upper respiratory tract Infections.
 Obstructive ventilatory defects
 Respiratory insuffiency.

AGAM PATHOLOGY
10. VIRAL PNEUMONIA:
 Causes
 Influenza virus Type A & B  Rhino Virus
 Respiratory Synctial Virus  Adeno Virus
 Human Metapneumovirus  Varicella virus
 Rubeola
 Influenza infection:
 Virulence Factors:
 Hemagglutinin (H1-H3) → Fuse with cell membrane → Release viral RNA
 Neuraminidase (N1, N2) → Budding of newly formed virions
 Virus entry into phagocytes → Inhibits Na channel → Electrolyte & Water balance →
Death of infected cell → Danger signal created → Macrophage activated →
Inflammtion exudates fill the alveolar lumen
 Human metapneumovirus:
 A paramyxovirus cause Bronchitis, Pneumonia and Acute respiratory tract infection.
 Detected by PCR for viral DNA & Direct Immunofluorescence.
 Ribavirin is treatment
 Clinical course :
 Severe URT Infection & Chestcolds.
 Fever, Headache, Muscle ache, Pain in legs & Cough may absent.
 Edema & Exudation – Disturb ventilation and Blood flow.
 Morphology :
 Process may be patchy, or it may involve whole lobes bilaterally or unilaterally.
 The affected areas are red-blue, congested and subcrepitant – Macroscopically.
 Mucosal hyperaemia, Lymphomonocytic and Plasmacytic infiltration of Submucosa.
 Alveolar spaces are free of cellular exudates.
 In Laryngotracheobronchitis , Broncholitics,Vocal cord swelling, Mucus production.
 Plugging of small airway → Focal Lung Atelectasis.
 Interstial inflammatory reaction is largely confined to wall of alveoli.
 Mononuclear inflammatory infiltrate of Lymphocytes & Macrophages are present.
 When complicated by ARDS, Pink Hyaline Membranes present.
 Complications :
 Abscess formation
 Empyema
 Bacteremic dissemination.
PATHOLOGY AGAM
11. PAN ACINAR EMPHYSEMA:
 Acini uniformly from Respiratory bronchiole to terminal blind alveoli.
 Commonly involve Lower Zones and Anterior Margins.
 Due α-1 Antitrypsin deficiency.

PATHOGENESIS:
 α-1 antitrypsin – Inhibitor of elastase
 Smoking → Inflammation → Neutrophil Recruitment → Release of Elastase → No
Antitrypsin → Excessive digestion of elastic tissue → Emphysema

MORPHOLOGY:
 Pale, voluminous lungs overlapping the heart.
 Large apical blebs /bullae are charecterstic of irregular emphysema 2o to scarring.
 Prolonged vasoconstriction leads to pulmunory arterial hypertension.
 Decrease in capillary bed area.
 Destruction of alveolar walls without fibrosis.
 Larger abnormal air spaces compress respiratory bronchioles and vasculature of lung.

CLINICAL COURSE:
 Dyspnoea
 Prominent Dyspnoea and adequate oxygenation of hemoglobin – pink puffers.
 Emphysema + pronounced chronic bronchitis + recurrent infections – patients retains
CO2 and become cyanotic – Blue bloaters.
 Secondary pulmonary hypertension.
 Cough /Wheezing
 Associated Bronchitis and Weight loss
 Impaired Expiratory Flow rate
 Death due to CAD, Respiratory failure, RHF, Collapse of lung.

TREATEMENT:
 Smoking cessation, O2 Therapy
 Bullectomy
 Alpha -1 AT Replacement.

AGAM PATHOLOGY
12. GOODPASTURE SYNDROME:
 Lung and Kidney injury caused by circulating Autoantibodies against Non-Collagenous
domain of alpha 3 chain of Collagen 4.
 Male preponderance.
 Majority of patients are active smokers.

PATHOGENESIS:
 Antibody initiate destruction and inflammatory of Basement membrane resulting in
Glomerulonephritis & Necrotizing hemorrhagic Interstial pneumonitis.
 Genetic predisposition [ HLA – DRB1*1501 and *1502]
 Anti – GBM antibody react with intrinsic antigen homogeneously.
 This antibody cross reacts with pulmonary basement membrane.

MORPHOLOGY:
 Lungs – Heavy with Red-Brown Consolidation due to diffuse Alveolar haemorrhage.
 Focal necrosis of alveolar walls with intra alveolar haemorrahages.
 Fibrous thickening of septae , Hypertrophy of Type 2 Pneumocytes , Organisation of
Blood in Alveolar spaces.
 Abundant hemosiderin due to earlier episodes of haemorrhage.
 Linear pattern of immunoglobulin deposition is the hallmark diagnostic finding.
 Focal proliferative Glomerulonephritis or Arsentic glomerulonephritis.

CLINICAL FEATURES:
 Hemoptysis
 Focal pulmunory consolidation
 Renal failure
 Cause of death is uremia.

TREATMENT:
 Plasmapheresis - removes offending antibodies.
 Immunosuppressive therapy - inhibit antibody production.
 Renal transplantation - severe renal disease.

PATHOLOGY AGAM
13. PNEUMOCONIOSIS
 It is the non-neoplastic lung reaction to inhalation of mineral dusts, organic and
inorganic particulates, chemical fumes and vapors from the workplace
 Etiology: occupational exposure to specific airborne agents, Air pollution
 Pathogenesis Its development depends on
 Amount of dust retain in lungs (duct concentration in air, duration of exposure,
effectiveness of clearance)
 Size, Shape and Buoyancy of particle (< 1-5 μm particle most dangerous)
 Particles solubility and Physio chemical reactivity (high solubility Rapid onset of lungs
damage low solubility evoke Fibrosis)
 Additional effects of other irritants

Dust Enters blood stream Systemic responses

Taken up by epithelial cell (or)

Interact directly with fibroblasts and interstitial macrophages (or)
Lymphatic drainage

Activation of innate and adaptive immunity

Inflammation and fibrosis

 Coal workers pneumoconiosis – lung disease cause by inhalation of coal particles and
other admired forms of dust. This may develop into:
 Asymptomatic Anthracosis – innocuous coal induced pulmonary lesion seen miners
 Simple coal workers pneumoconiosis little pulmonary dysfunction.
 Carbon macules and nodules accumulated in macrophages and collagen fibers
respectively
 Morphology: upper lobe and upper zone of lower lobe of lung are more
involved. Dilation of adjacent alveoli occurs leading to centrilobular emphysema
 Complicated coal workers pneumoconiosis (progressive massive fibrosis)
 Chronic exposure and intensely blackened scar of 1cm to 10 cm is seen.
 C/s: ↑ pulmonary dysfunction, pulmonary hypertension ,& cor pulmonale

AGAM PATHOLOGY
14. SILICOSIS
 It is a common lung disease caused by inhalation of crystalline Silicon dioxide (silica)
 Most prevalent chronic occupational disease that develops as slowly progressing
nodular fibrosing pneumoconiosis.
 Workers involving sandblasting and hard rock mining are at particularly high risk.

PATHOGENESIS
 Inhalation of silica particles
(crystalline form-more active fibrogenic, amorphous form – less active).
 Crystalline form quartz is most commonly implicated in silicosis.
 Macrophages phagocytose the silica particles → Activation of inflammasome and
release of inflammatory mediators like IL-1,IL-18, TNF → Inflammation → Fibrosis

MORPHOLOGY
 Gross- early stage :tiny discrete blackened nodule in hilar lymph nodes and upper zone
of lungs
 Late stage: nodule coalesce into collagenous scar ,fibrotic lesions in hilar lymph nodes
and pleura ,sheets of calcification of lymph nodes (eggshell calcification )
 M/s- hall mark lesion with central area of whorled hyalinised collagen fibers, peripheral
zone with dust laden macrophages, polarized microscopy reveals weekly birefringent
silica particles.

CLINICAL COURSE:
 chest radiography- modularity in upper zones of lungs
 Disease may worsen even if exposure is stops. Slow to kill, impairs pulmonary function
 Develop pulmonary hypertension and cor pulmonale as a result of chronic hypoxia
induced vasoconstriction and parenchymal destruction.
 Often Associated with TB - Central zone of caseation.
 Slow and insidious onset 10 to30 years, high risk of cancer

PATHOLOGY AGAM
15. SARCOIDOSIS:
 Sarcoidosis is a multisystem disease of unknown etiology.
 Characterized by Noncaseating granulomatous inflammation.
 Organs involved: lung, lymph node, liver, skin, eye
 Affects 20 – 40 years of age. More common in women than men.
 Higher prevalence among non-smokers, an association that is virtually unique to
sarcoidosis among pulmonary diseases
 Etiology :
 Genetic predisposition – HLA class II halo type, HLA – A1 , HLA –B8
 Exposure to environmental agents
 Cellular immune response
PATHOGENESIS: Unknown Antigen

Taken by APC & present to T cells

Proliferation of CD4+ Helper T cells & Activated monocytes

Release of Cytokines (IL-2, IFN)

Formation of Granuloma

CLINICAL FEATUES:
 Lung : Advanced cases , small palpable nodules present .Granulomas in the interstitium
along the lymphatics, around bronchi and blood vessels. 5-15% patients -Honey comb
lung seen - diffuse interstitial fibrosis.
 Lymph node: Intrathoracic hilar and paratracheal lymph nodes enlarged. Painless, firm,
rubbery texture. Lymph nodes are nonmatted and do not ulcerate.
 Skin: Erythema nodosum – red, tender nodules on the anterior aspect of the legs.
 Eye & lacrimal: Iritis , choroiditis , retinitis , optic nerve involvement. Sicca syndrome.
 Unilateral aur bilateral parotitis with painful enlargement of the parotid gland.
 Develop Xerostomia combined with uveoparotid involvement – Mikulicz syndrome.
 Liver and spleen and bone marrow are also involved.
 Hypercalcemia and hypercalciuria caused by increase calcium absorption.

AGAM PATHOLOGY
MICROSCOPY:
 Non necrotizing epitheloid granuloma – compact collection of epithelioid cells formed
by an outer zone rich in CD4 + T cells.
 Naked granulomas – peripheral rim of lymphocytes are absent
 Cytoplasmic inclusions :
 Schaumann bodies – concentric laminations of calcium and proteins
 Asteroid bodies – stellate inclusions enclosed within giant cells.
DIAGNOSIS:
 Chest X ray – bilateral hilar lymphadenopathy
 Histological diagnosis – noncaseating granuloma
 Serum Angiotensin – converting enzyme (ACE) –elevated

16. ASBESTOSIS / PARENCHYMAL INTERSTITIAL FIBROSIS

 Asbestos is a family of crystalline hydrate silicate that are associated with pulmonary
Fibrosis carcinoma mesothelioma and other cancers
 It is a lung disorder caused by inhalation of crystalline hydrated silicates (asbestos)
PATHOGENESIS
 Disease causing capability of different forms of asbestos depends on concentration size,
shape and solubility
 Asbestos - 2 geometric form
 Serpentine chrysotile -90% used in industries. More flexible and curled structure
are settled in upper respiratory passage and removed by mucociliary elevators (less
pathogenic)
 Amphiboles – less prevalent more pathogenic. Strait and stiff amphiboles align
themselves in the airstream and transported to deeper tissues, penetrate
epithelium and interstitium
 Amphibole and serpentine are fibro genic and increasing doses are associated with
higher incidence of asbestos related disorders.
 In contrast asbestos act as tumor initiator and Promoter its oncogenic effects mediated
by reactive free radicals from asbestos fibers, localize it in distal lungs close to
mesothelium layer.
 Smoking also enhances the effect of asbestosis (asbestos exposure and smoking
together led to a define fold increasing the risk of carcinoma).
 Eventually leading to generalized interstitial pulmonary inflammation and interstitial
Fibrosis.
PATHOLOGY AGAM
MORPHOLOGY
 Asbestosis is marked by different pulmonary interstitial Fibrosis containing multiple
asbestos bodies
 Asbestos bodies- golden brown fusiform beaded rods
 Asbestosis begins as fibrosis around the respiratory bronchioles alveolar ducts and
extend to adjacent alveolar sac and alveoli
 Plural plaques -common manifestation of asbestos exposure;
 these are well circumscribed plaque of dense collagen that are often calcified
 developed frequently on anterior and poster lateral surface of parietal pleura and
domes of diaphragm
 They do not determine the time of exposure and level of exposure and do not
contain asbestos bodies
 Induce plural effusion that are serous or bloody, diffuse plural Fibrosis may also
occur binding lungs to the thoracic wall
 Both lung carcinoma and mesotheliomas in workers exposed to asbestos

CLINICAL COURSE:
 Dyspnea on exertion - 1st manifestation--- later dyspnea on rest.
 Cough associated with sputum (due to smoking than asbestosis)
 Chest x-ray – irregular linear density particularly in lower lobes of lungs
 the disease may progress to respiratory failure cor pulmonale and death
 pleural plaques asymptomatic
 Complications- carcinoma of lung
 Risk factor – concomitant cigarette smoking.
 Lung cancer or pleural cancer associated with asbestos exposure carries a particular
poor prognosis.

ASBESTOS RELATED DISORDERS

 Localized fibrous plaques or diffuse pleural Fibrosis
 Pleural effusion
 Parenchymal interstitial Fibrosis
 Lung carcinoma
 Mesotheliomas
 Laryngeal, ovarian and other extra pulmonary neoplasm, increased risk of
cardiovascular and systemic autoimmune diseases

AGAM PATHOLOGY
17. SARCOID GRANULOMA:
Systemic granulomatous disease of unknown cause.
PATHOGENESIS:
 Disordered immune regulation in genetically predisposed individuals.
 Immunological factors:
 High levels of CD4-T cells in intra-alveolar and interstitial accumulation.
 Increased levels of IL-2 and INF-gamma- T-cell expansion and macrophage activation.
 Impaired dendritic cell function.
 Marker: TNF concentration in bronchoalveolar fluid.
MORPHOLOGY:
 Non-caseating granulomas, giant cells contain Schaumann bodies and Asteroid bodies.
 Bilateral hilar lymphadenopathy, stages of fibrosis and hyalinization found.
 Splenomegaly, hepatomegaly contains scattered granulomas more in portal triad than in
lobar parenchyma.
 Skin lesions-erythema nodosum, painless subcutaneous nodules.
 Ocular involvement-sicca syndrome (dry eyes), iritis or iridocyclitis, corneal opacity,
glaucoma and total loss of vision.
 Bilateral sarcoidosis of parotid, submaxillary, sublingual- Uveoparotid involvement-
Mikulicz syndrome
 Involves heart, kidney, CNS and endocrine glands.

18. HYPERSENSITIVITY PNEUMONITIS:

 Immunologically mediated inflammatory lung disease that affects the alveoli and often
called as allergic alveolitis.
 Sources of antigens causing hypersensitivity pneumonitis :
 Mushrooms , fungi , yeasts
 Bacteria
 Mycobacteria
 Birds – pigeons , dove feathers , ducks , parakeets
 Chemicals – Isocyanates, zinc, dyes.
 It manifests predominantly as a restrictive lung disease with the typical decrease in
diffusion capacity, lung compliance and total lung volume.
 Loose, poorly formed granulomas without necrosis are present in a very bronchiolar
location.
 In advanced cases – bilateral, upper lobe dominant interstitial fibrosis occurs.
PATHOLOGY AGAM
19. COR PULMONALE:
Right-sided hypertensive heart disease / Right ventricular pressure overload.
DISORDERS PREDISPOSING TO COR PULMONALE:
 Disease of parenchyma:
 COPD
 Diffuse interstitial pulmonary disease
 Pneumoconiosis
 Cystic fibrosis
 Bronchiectasis
 Disease of pulmonary vessels
 Recurrent pulmonary thromboembolism
 Primary pulmonary hypertension
 Extensive pulmonary arteritis
 Drug, toxin, radiation- vascular obstruction
 Extensive pulmonary tumour microembolism
 Disorders affecting chest movements:
 Kyphoscoliosis
 Obesity ( sleep apnoea, pickwickian syndrome)
 neuromuscular disease
 Disorders inducing pulmonary arterial constriction:
 Metabolic acidosis
 Hypoxemia
 Chronic altitude sickness
 Obstruction in major airways
 Idiopathic alveolar hypoventilation
MORPHOLOGY:
 Acute cor pulmonale:
 Marked dilation of right ventricle without hypertrophy
 Dilated ovoid shape on cross section.
 Chronic cor pulmonale:
 Right ventricular hypertrophy, thickening of muscles of outflow tract, thickening
of moderator band, muscle bundle that connects ventricular septum to anterior
papillary muscle.
 Regurgitation and fibrous thickening of tricuspid valve

AGAM PATHOLOGY
SHORT NOTES
1. REID’S INDEX:
 The magnitude of the increase in size is assessed by the ratio of the thickness of the
submucosal glands layer to that of the bronchial wall.
 Ratio: thickness of the submucosal mucous glands layer : thickness between epithelium
and cartilage that covers the bronchi.
 Use: Detect hypertrophy and hyperplasia of mucus glands in chronic bronchitis.
 Nomal value : <0.4 ; Increased in chronic bronchitis

2. BYSSINOSIS:
 Interstitial lung disease caused by organic dust (eg: cotton fibres, hemp etc. ).
 The chief symptoms are cough, wheezing, shortness of breath and chest tightness.
 Associated with hypersensitive pneumonitis.
 Occupational lung disease.
 Smoking significantly exacerbates byssinosis.

3. FERRUGINOUS BODIES:
 Histological finding in interstitial lung disease.
 Cause: Asbestos exposure
 Occupation associated: ship building, roofing, plumbing and construction.
 Morphology:
 Small golden-brown bodies in the septum of alveolus.
 Fibres of asbestos coated with an iron rich material derived from ferritin and
hemosiderin.
 They arise when macrophage phagocytose asbestos fibres.

PATHOLOGY AGAM
UPDATES
1. ASTHMA:
 Definition: Asthma is a heterogeneous disease, usually characterized by chronic airway
inflammation and variable expiratory airflow obstruction that produces symptoms such as
wheezing, shortness of breath, chest tightness, and cough, which vary over time and in
intensity.
 Mediators- IL-5, antagonists of which are effective in treating severe forms of asthma that
are associated with peripheral blood eosinophilia; and galectin-10 (GAL10), which is
released from eosinophils and forms crystals known as Charcot-Leyden crystals. Long
recognized as a feature of asthma, recent studies have shown that these crystals are strong
inducers of inflammation and mucus production.
 Genetic susceptibility- Variants associated with the genes encoding IL-33, a member of the
IL-1 family of cytokines, and its receptor, ST2, which induce the production of Th2 cytokines;
Variants associated with the gene encoding thymic stromal lymphopoietin (TSLP), a cytokine
produced by epithelium that may have a role in initiating allergic reactions.
 Therapy is based on the severity of the disease. The centerpieces of standard therapy are
bronchodilators, glucocorticoids, and leukotriene antagonists. For severe and difficult-to-
treat asthma in adolescents and adults, novel biologic therapies targeting inflammatory
mediators such as IL-5 blocking antibodies, which is effective in severe asthma associated
with Th2 immune responses and peripheral blood eosinophilia, are now available
2. BRONCHIECTASIS:
 Haemophilus influenzae is found in approximately half and Pseudomonas aeruginosa in 12%
to 30% of sputum cultures from patients with bronchiectasis, with four other types of
bacteria (including non-tuberculous mycobacteria) making up most of the remaining cases
in patients from different geographic locations.
 This observation suggests that the inflamed, mucoid, sometimes anaerobic, bronchiectatic
microenvironment favors colonization by a relatively few microbial species.
 In allergic bronchopulmonary aspergillosis, fungal hyphae can be seen on special stains
within the mucoinflammatory contents of the dilated segmental bronchi.
 In late stages the fungus may infiltrate the bronchial wall.
3. IDIOPATHIC PULMONARY FIBROSIS:
 Mutations in the TERT, TERC, PARN, and RTEL1 genes, all of which are involved with the
maintenance of telomeres, are associated with increased risk of IPF.
 Usually there is slowly progressive respiratory failure, but some patients have acute
exacerbations and follow a rapid downhill clinical course.
 Two drugs, a tyrosine kinase inhibitor and a TGF-ß antagonist, have both been shown to slow
disease progression and represent the first effective (albeit modestly so) targeted therapies
for IPF.

AGAM PATHOLOGY
4. PULMONARY ALVEOLAR PROTEINOSIS:
 The alveolar precipitate is pink, homogeneous, and periodic acid–Schiff–positive.
 Primary disease is treated with GM-CSF replacement therapy, sometimes followed by
allogeneic hematopoietic stem cell transplantation, which can be curative.

5. PROCALCITONIN:
 Procalcitonin, an acute-phase reactant produced primarily in the liver, is more significantly
elevated in bacterial than viral infections and has some predictive value, but is not specific,
as it is also markedly elevated in other severe inflammatory disorders, such as systemic
inflammatory response syndrome (SIRS).

6. CORONA VIRUS
 Coronaviruses are enveloped, positive-sense RNA viruses that infect humans and several
other vertebrate species.
 Weakly pathogenic coronaviruses cause mild cold-like upper respiratory tract infections,
while highly pathogenic ones may cause severe, often fatal pneumonia.
 An example of a highly pathogenic type is SARS-CoV-2, a strain that emerged in late 2019 in
China that is producing a still evolving pandemic as of early 2020.
 Highly pathogenic coronaviruses like SARS-CoV-2 bind the ACE2 protein on the surface of
pulmonary alveolar epithelial cells, explaining the tropism of these viruses for the lung.
 With highly pathogenic forms in susceptible hosts, typically older individuals with comorbid
conditions, the host immune response and locally released cytokines often produce acute
lung injury and ARDS.

7. TUMORS:
 The relative proportions of the major categories are: Adenocarcinoma (50%), Squamous cell
carcinoma (20%), Small cell carcinoma (15%), large cell carcinoma (2%), other (13%)
 Thus combinations of squamous cell carcinoma and adenocarcinoma or small cell and
squamous cell carcinoma occur in about 14% and 5% of patients, respectively.
 This simplistic idea is challenged, by the existence of tumors comprised of a mixture of small
cell carcinoma and other histologies and well-documented “transformations” of non–small
cell carcinoma to small cell carcinoma.

8. SMOKING PREVENTION
 The best “treatment” for lung cancer is smoking prevention.
 This reality has led to early detection trials in high-risk individuals using low-dose computed
tomography, which is capable of detecting some early (resectable) non–small cell lung
cancers, but at a cost of a high incidence of false-positive (noncancer) finding.

PATHOLOGY AGAM
9. TREATMENT OF SMALL CELL CARCINOMA
 Small cell carcinoma is sensitive to radiation therapy and chemotherapy, and 10% of patients
with limited disease survive for 5 years and may be cured.
 Unfortunately, most patients present with advanced stage disease; for these patients,
despite excellent initial responses to chemotherapy, the median survival is approximately
10 months and the cure rate is close to zero.

10. PULMONARY HAMARTOMA:

 It is a clonal neoplasm associated with chromosomal aberrations involving either 6p21 or
12q14-q15.
 These aberrations are found in the mesenchymal component, while the epithelial
component appears to represent entrapped respiratory epithelium.

11. MALIGNANT MESOTHELIOMA MUTATIONS

 Sequencing of mesothelioma genomes has shown that driver mutations are common in the
NF2 (neurofibromatosis-2) gene, which encodes a cell signaling regulator; and BAP1, which
encodes a protein that interacts with the BRCA1 tumor suppressor and appears to function
as a chromatin regulator.
 Of note, individuals with germline mutations in BAP1 have a markedly elevated risk of
mesothelioma, further implicating this tumor suppressor gene in the pathogenesis of the
disease; Wilms tumor 1 (WT-1), cytokeratin 5/6, and podoplanin, and unlike
adenocarcinomas, are negative for Claudin4.
 This panel of antibodies is diagnostic in a majority of cases when interpreted in the context
of morphology and clinical presentation.

12. ONE LINERS

 Carbon deposits are dark black in color and are readily visible grossly and microscopically.
 In its most severe form, chronic radiation pneumonitis and associated progressive fibrosis
can lead to cyanosis, pulmonary hypertension, and cor pulmonale
 Histologic changes in Hypersensitivity Pneumonitis depend on the phase of the disease;
acute alveolar damage is seen in the first hours and few days after antigen exposure, while
subacute changes are characteristically centered on bronchioles.
 In hemodynamically stable patients with a low to moderate risk of pulmonary embolism, D-
dimer measurement is a useful screening test, as a normal D-dimer level excludes pulmonary
embolism.
 Chewing tobacco is not a safe substitute for smoking cigarettes or cigars, as these products
spare the lung but cause oral cancers and can lead to nicotine addiction.
 The long-term effects of electronic cigarette aerosols are not known, as “vaping” is a
relatively recent phenomenon.
AGAM PATHOLOGY
 Adenocarcinoma is associated with tobacco smoking, but less so than other histologic
subtypes; as a result, it is the most common subtype in never-smokers.
 Adenocarcinomas also have gain-of-function mutations in serine/threonine kinases (BRAF,
2% of tumors, and PI3K, 2% of tumors) or in the KRAS gene (roughly 30% of tumors), all of
which encode signaling molecules that lie downstream of receptor tyrosine kinases in
growth factor signaling pathways.
 Loss of chromosome 3p occurs in nearly all of Small cell Carcinoma and is seen even in
histologically normal lung epithelium, suggesting that this also is a critical early event. This
subtype is also commonly associated with amplification of genes of the MYC family

CLICK HERE FOR FEEDBACK

PATHOLOGY AGAM