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MEETING THE EXPERT SESSION

DEPARTMENT OF PATHOLOGY, UKMMC

TOPICS: Respiratory Malignancies, Obstructive Pulmonary Diseases, Pleural Diseases

LECTURER: AP. Dr. Wong Yin Ping

DATE: 20.12.2022

TIME: 10:30am – 12:30pm

Case 1

A 50-year-old non-smoker woman presented with recurrent seizure. Upon questioning,

she had one-month history of chronic cough with associated significant loss of weight and
loss of appetite. MRI brain showed multiple brain lesions. Subsequent chest x-ray showed
a peripheral lung mass. Her condition worsened and died. An autopsy was performed.

Exhibit A: Gross picture of the deceased’s right lung.

Exhibit B: Histological section from the deceased’s lung mass.

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a. Describe the gross findings in Exhibit A.

- Presence of fairly circumscribed, tan tumour mass
- Located at peripheral lung region.
- Areas of hemorrhage are also noted.

b. Describe the histological features seen in Exhibit B.

- Presence of malignant cells forming glandular architecture
- The malignant cells exhibit nuclear pleomorphism, hyperchromatic to vesicular nuclei
with prominent nucleoli, intracellular mucin is seen.

c. What is your diagnosis?

Lepidic predominant adenocarcinoma. (metastatic tumour, glandular-forming tumour).
Adenocarcinoma of the lung.

d. What is the probable nature of the brain lesion?

Brain metastases.

e. Discuss briefly the metastatic spread of lung carcinomas in general.

- Metastatic spread to opposite lung, bone, liver, brain, adrenal, regional lymph nodes.
- Symptoms of metastases depending on site of metastases: back pain in bone mets,
hemiparesis, cranial nerve damage, seizures in brain mets, loss if weight, loss of
appetite, abdominal discomfort, with/without jaundice in liver mets.

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Case 2

A 60-year-old heavy smoker man presented with 3 weeks history of chronic cough with
haemoptysis. Physical examination revealed his right eye ptosis. Chest x-ray showed
apical lung lesion. A biopsy of the lung lesion was performed.

Exhibit A: Histological section of the lung lesion.

a. Describe the histological features seen in Exhibit A.

- Sheets of malignant squamous epithelial cells.
- The malignant cells exhibit nuclear pleomorphism, hyperchromatic to vesicular nuclei
with prominent nucleoli.
- Keratinpearl, individual keratinization and intercellular bridges are seen.
*poorly differentiated: lacking keratinization.

b. What is your diagnosis?

Well-differentiated squamous cell carcinoma.
Squamous cell carcinoma of the lung.

c. What do you think has happened to his right eye? What are the other expected
findings in his right eye? Explain briefly its pathogenesis.
- Patient is having Horner syndrome.
- The patient shows symptoms like miosis, anhidrosis, enophthalmos.
- Pathogenesis: Apical lung cancer that invades neural structures around trachea,
including cervical sympathetic plexus, thus the tumour is known as Pancoast tumours.

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Case 3

A 40-year-old heavy smoker man was admitted for confusion and delirious secondary to
hyponatremia. Chest x-ray revealed a mass at right hilar region. His condition worsened
and died. An autopsy was performed.

Exhibit A: Gross picture of the right lung.

Exhibit B: Histological section of the lung mass.

a. Describe the gross findings seen in Exhibit A.

- Cut surface is soft, lobulated, and white to tan appearance.
- The tumour causes obstruction of the left main bronchus so that the distal lung is
collapsed, atelectatic.
- Huge whitish irregular tan tumour
- At the hilar region extending into upper and lowerlobes.

b. Describe the histological findings seen in Exhibit B.

- Sheets of small round blue malignant cells.
- The malignant cells exhibit hyperchromatic nuclei with inconspicuous nucleoli.
- Nuclear molding, apoptotic bodies are easily seen.
- Mitosis is hardly seen. Necrosis can be seen.

c. What is your diagnosis?

Small cell carcinoma of the lung.

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d. Explain briefly how hyponatremia can occur in this patient.

- Small cell carcinoma is commonest associated with ectopic hormone production, known
as paraneoplastic syndrome.
- Due to SIADH (syndrome of inappropriate anti-diuretic hormone) secretion.
- Related to excessive secretion of anti-diuretic hormone (ADH) predominantly by small
cell carcinoma will prevent the excretion of water.
- More water is reabsorbed into blood circulation, leading to inappropriate water retention
in body.
- Thus, concentrated urine will be produced and retention of sodium in body will decrease.
- Sodium will become diluted in the blood leading to hyponatremia.

e. Discuss briefly the effects and complications of lung carcinomas in general.

- Local effects usually among patients above 50s. Clinical features:
• cough (involvement of central airways)
• hemoptysis (hemorrhage from tumour in airway), chest pain (extension of tumour into
mediastinum, pleura or chest wall), dyspnoea
• pneumonia, abscess, lobar collapse (airway obstruction by tumour)
• lipoid pneumonia (tumour obstruction, accumulation of cellular lipid in foamy
macrophages)
• pleural effusion (tumour spread into pleura)
• hoarseness (Recurrent laryngeal nerve invasion)
• dysphagia (esophageal nerve invasion)
• diaphragm paralysis (phrenic nerve invasion)
• rib destruction (Chest wall invasion)
• SVC syndrome (SVC compression by tumour)
• Horner syndrome (sympathetic ganglia invasion)
• pericarditis, tamponade (pericardial involvement)
- Paraneoplastic syndrome. Symptoms complexes in cancer patients not explained by
tumour or secretion of hormones indigenous to the tissue. Clinical effects:
• Hyponatremia due to antidiuretic hormone (ADH) secretion,
• Cushing disease due to adrenocorticotropic hormone (ACTH) secretion,
• Hypercalcemia due to parathormone, parathyroid hormone-related peptide (PTH-rP)
secretion,
• Hypocalcemia due to calcitonin secretions,
• Gynaecomastia due to gonadotrophins secretions,
• Carcinoid syndrome due to secretions of histamine and bradykinin.
- Other systemic manifestations include:
• Lambert-Eaton myasthenic syndrome: muscle weakness due to autoantibodies directed
to neuronal calcium channel,
• Peripheral neuropathy: usually purely sensory,
• Dermatologic abnormalities: acanthosis nigricans,
• Haematologic abnormalities: leukemoid reactions, hypercoagulable states,
• Connective tissue abnormalitites: hypertrophic pulmonary osteoarthropathy, cause
clubbing of fingers.
- Distance metastases. The tumour spread to liver, adrenal glands, bones and brain. The
symptoms of metastases depend on site. Bone metastases causes back pain, brain
metastases causes hemiparesis, cranial nerve damage and seizures, liver metastases
causes loss of appetite and unexplained weight loss.

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Case 4

A 34-year-old man presented with worsening dyspnoea following two days history of
productive cough and fever. Physical examination revealed expiratory rhonchi on
auscultation. Sputum was sent for laboratory workup.

Exhibit A (i) & (ii): Sputum smears of the patient.

a. Name the smear findings.

- Cruschmann spirals: shed epithelium with spiral-shape and thread-like structure.
- Charcot Leyden crystals: eosinophilic protein with pointing ends.

b. What is the likely diagnosis?

Acute exacerbation of bronchial asthma.

c. Define the diagnosis in (a) and its pathogenesis.

- Definition: chronic inflammatory disorder of airways which is reversible and marked by
episodic bronchoconstriction due to airway hyperresponsiveness to noxious stimuli. It is
clinically characterized by recurrent episodes of wheezing, dyspnoea and coughing.
- Pathogensis:
• Type 1 (IgE-mediated) hypersensitivity reaction. A form of exaggerated TH2
response to normally harmless environmental antigens in genetically
predisposed individuals.
• Presensitized state: exposure to allergen elicit a TH2-dominated response favouring
IgE production and eosinophil recruitment.
• On re-exposure to similar allergen, the immediate reaction is triggered by Ag-
induced cross-linking of IgE bound to Fc receptors on mast cells.
• These cells release preformed mediators that directly and via neuronal reflexes
induce bronchospasm, increased vascular permeability, mucous production, and
recruitment of leukocytes.
• Leukocytes recruited to the site of reaction (neutrophils, eosinophils, lymphocytes)
release additional mediators that initiate late phase of asthma causing epithelial
damage and bronchospasm.

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Case 5

A 50-year-old heavy smoker man, newly diagnosed chronic obstructive pulmonary

disease (COPD), presented with sudden onset of right sided chest pain associated with
difficulty in breathing. Physical examination revealed hyperinflated lung with reduced
air entry of the right lung on auscultation.
a. What do you think is the cause of his acute clinical presentations?
Pneumothorax.

His condition worsened and died. An autopsy was performed.

Exhibit A: Gross picture of the deceased’s lung.

Exhibit B: Histological section of the deceased’s lung.

b. Describe the gross findings in Exhibit A.

- Large multiple subpleural bullae on lung surface as large, dilated airspaces bulge out from
beneath the pleura of the hyperinflated lungs.
- Loss of lung parenchyma by destruction of alveoli so that there is permanent dilation of
airspaces with loss of elastic recoil.

c. Describe the histological findings in Exhibit B.

- Abnormally large, dilated alveoli are separated by thin septa with evidence of destruction
of alveoli wall.

d. What is your diagnosis? Explain briefly its pathogenesis.

- Emphysema.
- Pathogenesis: smoking/air pollutant + genetic predisposition > (1) oxidative stress,
increased apoptosis & senescence, (2) inflammatory cells release of inflammatory
mediators, (3) imbalance protease & anti-protease > all attribute to alveolar wall
destruction.
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e. Name the effects and complications of COPD in general.

- Effects: dyspnoea, cyanosis (in chronic bronchitis), prone to infection
- Complications: pneumothorax, secondary pulmonary hypertension, cor pulmonale,
respiratory failure.

Case 6

A 15-year-old teenage girl, known case of cystic fibrosis, presented with fever, chronic
cough associated with copious foul-smelling sputum. Her condition deteriorated with
dyspnoea and cyanosis and died. An autopsy was performed.

Exhibit A: Gross picture of the deceased’s lung.

a. Describe the gross findings in Exhibit A.

- Cystically dilated airways (bronchi & bronchioles) with mucopurulent exudate
- Mainly affects the lower lobe.
- Distal airway distention mediated by inflammation and airway destruction.

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b. What is your diagnosis?

Bronchiectasis

c. Define the diagnosis in (b) and explain briefly its causes and pathogenesis in
general.
- Definition: permanent dilatation of bronchi and bronchioles due to destruction of
smooth muscle and elastic tissue associated with chronic necrotizing infections.
- Causes:
1. congenital/ hereditary conditions: cystic fibrosis, primary ciliary dyskinesia,
kartagener syndrome.
2. Infections: necrotizing pneumonia by bacteria, viruses, fungi
3. Bronchial obstruction: tumour, foreign bodies, mucous impaction
4. Others: SLE, rheumatoid arthritis, inflammatory bowel disease
5. Idiopathic.
- Pathogenesis:
Pre-requisite: bronchial obstruction + severe infection of bronchi.
Bronchial obstruction > normal clearing mechanisms are impaired > pooling ofsecretion
distal to the obstruction & secondary infection & inflammation.
Severe infection of bronchi > inflammation, often with necrosis, fibrosis & eventually
dilatation of airways.

d. Discuss the effect and complications of the diagnosis in (b).

- Effects: severe, persistent postural cough with copious foul-smelling sputum,
haemoptysis, fever, clubbing
- Complications: cor pulmonale, metastatic brain abscess, amyloidosis.

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Case 7 (MEQ)

A 50-year-old man, recently admitted for myocardial infarction, presented with

progressive dyspnoea on exertion with associated bilateral pedal oedema. Chest x-ray
showed evidence of bilateral pleural effusion.
a. Define pleural effusion.
Accumulation of fluid (>15mls) within the pleural space.

b. What are the types of pleural effusion, diagnostic criteria and their causes
/associated conditions?
i) Types of pleural effusion: exudative, transudative
ii) Causes/associated conditions:
• Transudative: congestive heart failure, liver cirrhosis, nephrotic syndrome,
chronic kidney disease, protein losing enteropathy.
• Exudative: inflammatory disease of lung (tuberculosis, pneumonia, lung
abscess, bronchiectasis), pleural lesions (metastatic tumour to pleura,
primary pleural tumours), others malignancy, connective tissue diseases
(SLE, rheumatoid arthritis), uremia
• Others: haemothorax- due to major trauma/ruptured aortic aneurysm,
chylothorax-due to tumour obstruction of normal lymphatics.
iii) Diagnostic criteria: Light’s criteria
Transudative Exudative

< 0.5 >0.5

ratio

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