GC077 Pleural Effusion In A Chronic Smoker
Accumulation of fluid in the pleural space in a chronic smoker, most commonly due to underlying malignancy (such as lung cancer or mesothelioma), though infectious, cardiac, and other etiologies must also be considered.
Pleural Effusion in a Chronic Smoker — Lung Cancer
Big Idea: A chronic smoker presents with pleural effusion. The differential diagnosis is broad, but in this clinical context the lecture takes you on a journey from understanding the pathophysiology of pleural fluid accumulation → to investigating the effusion → discovering it is exudative with atypical cells → pursuing tissue diagnosis → confirming lung cancer (specifically adenocarcinoma) → understanding staging, molecular testing, and the modern treatment landscape of non-small cell lung cancer (NSCLC). This is a classic "one symptom, one deadly diagnosis" lecture that threads together respiratory medicine, oncology, and data interpretation.
Learning Objectives [1]:
- Learn the pathophysiology, common causes and investigations of pleural effusion
- Understand the pathology and natural history of lung cancer, and cigarette smoking as the predominant cause
- Understand the symptoms and signs of lung cancer with reference to the anatomy of the thoracic structures and cancer metastasis
- Learn the principles of investigations, staging and treatment of lung cancer
How it fits in: This lecture bridges GC 012 (abnormal lung shadow), GC 041 (COPD/smoking cessation), GC 083 (construction site worker – occupational lung disease), and GC 084 (SOB on exertion). It is the lung cancer lecture of the General Clerkship. Expect exam questions on Light's criteria, clinical features of lung cancer by anatomical location, TNM staging principles, molecular targets (EGFR, ALK), and the distinction between transudative and exudative effusions.
M/64, chronic smoker, retired restaurant waiter [1]
- Presents with pleural effusion
- Diagnostic + therapeutic thoracentesis × 2
- Exudative changes
- Atypical cells with large nuclear-to-cytoplasmic (N/C) ratio — need to rule out malignancy
- Non-diagnostic pleural fluid cytology and percutaneous biopsy — meaning the initial cytology did NOT definitively show cancer, and even a percutaneous (needle) biopsy was non-diagnostic
This case illustrates a critical real-world point: pleural fluid cytology has limited sensitivity (~60% first tap, ~75% with 2 taps) [3]. When cytology is non-diagnostic but suspicion for malignancy remains high, you must escalate to more invasive tissue sampling (pleuroscopy/thoracoscopy, EBUS-TBNA, or endobronchial biopsy).
Part 1: Pleural Effusion — Pathophysiology, Causes, and Investigation
The pleural space normally contains a tiny amount of fluid (~5–15 mL) that acts as a lubricant between the visceral and parietal pleura. The balance of fluid in this space depends on four key forces [1]:
| Force | Direction | Explanation |
|---|---|---|
| 1. Hydrostatic pressure | Drives fluid OUT of the vascular compartment INTO the pleural space | Like water pressure in a pipe — the higher the pressure, the more fluid leaks out. Elevated in heart failure. |
| 2. Oncotic pressure | Keeps fluid IN the vascular compartment | Proteins (mainly albumin) in the blood act like sponges, holding water inside vessels. Reduced in hypoalbuminaemia (cirrhosis, nephrotic syndrome). |
| 3. Lymphatic drainage | Removes fluid FROM the pleural space | Lymphatics on the parietal pleura absorb excess pleural fluid. Blocked by tumour, inflammation, or fibrosis. |
| 4. Capillary permeability | Controls leak rate | Increased permeability (inflammation, infection, malignancy) allows more protein and fluid to escape into the pleural space. |
Additionally, the lecture mentions small holes in the diaphragm [1] — these are actual anatomical fenestrations that allow communication between the peritoneal and pleural cavities. This explains:
- Hepatic hydrothorax in cirrhosis (ascitic fluid tracks up through diaphragmatic defects) [7]
- Peritoneal dialysis-related pleural effusion (PD fluid leaks into the thorax) [4]
Why do we get pleural effusion?
Pleural effusion = imbalance in Starling forces OR impaired lymphatic drainage OR increased capillary permeability OR fluid tracking from the peritoneum. The pathophysiology directly determines whether the effusion is transudative or exudative.
Light's Criteria: Pleural fluid is EXUDATIVE if ANY ONE of the following is met [2]:
- Pleural fluid / serum protein ratio > 0.5
- Pleural fluid / serum LDH ratio > 0.6
- Pleural fluid LDH > 2/3 of upper limit of normal (ULN) of serum LDH
Why this matters from first principles:
- A transudate is caused by systemic factors (↑hydrostatic pressure or ↓oncotic pressure) — the pleural membranes themselves are healthy, so protein and LDH don't leak across. The fluid is "clear" and protein-poor.
- An exudate is caused by local pleural/lung disease (inflammation, infection, malignancy) — damaged capillaries or inflamed pleura leak protein and cellular enzymes (LDH) into the fluid. The fluid is protein-rich.
| Feature | Transudate | Exudate |
|---|---|---|
| Mechanism | Systemic ↑hydrostatic or ↓oncotic | Local pleural/lung disease |
| Common causes | Heart failure, cirrhosis, nephrotic syndrome, hypothyroidism, peritoneal dialysis | Malignancy, infection (pneumonia, TB, empyema), PE, connective tissue disease (RA, SLE), pancreatitis [2][6] |
| Protein | Low | High |
| LDH | Low | High |
Exam Trap: Light's Criteria
Light's criteria tend to overdiagnose exudates, especially in patients on chronic diuretics (who concentrate the protein in pleural fluid). If the fluid just barely meets exudative criteria and you suspect transudate, check if serum − pleural fluid albumin gradient > 1.2 g/dL (suggests transudate) or serum − pleural fluid protein < 3.1 g/dL (suggests exudate) [2].
Once you've confirmed the effusion is exudative, you need to narrow the cause:
| Test | Finding | Significance |
|---|---|---|
| pH | < 7.30 | Empyema, malignancy, TB, RA/SLE, oesophageal rupture |
| Glucose | Low (lower than blood) | Same as low pH causes — organisms/cells consuming glucose |
| LDH | > 1000 IU/L | Empyema, malignancy, RA, paragonimiasis [2] |
| Cell count | Neutrophil predominant | Acute inflammation: parapneumonic, PE, abdominal disease |
| Cell count | Lymphocyte predominant | Chronic inflammation: malignancy, TB, RA/SLE [3] |
| Cytology | Malignant cells | Malignant effusion (sensitivity ~60% first tap, ~75% with 2 taps) |
| ADA | > 40 U/L | TB pleurisy (90% sensitivity) [5] |
| Microbiology | Gram stain, AFB smear, culture | Bacterial infection, TB |
| Cholesterol | > 4 g/dL, milky | Chylothorax (lymphatic obstruction/damage) |
| Amylase | Elevated | Pancreatitis, malignancy, oesophageal rupture |
| Bloody | Frank blood | Traumatic, malignancy, TB, PE |
In the index case: exudative effusion + atypical cells with large N/C ratio → suspicion for malignancy [1]
Step 1: Imaging
- CXR: Meniscus sign or blunted costophrenic angle (requires ~200 mL to be visible) [3]
- Ultrasound: More sensitive than CXR; can detect loculated effusions, guide thoracentesis
- CT ± PET/CT if malignancy suspected or initial tap non-diagnostic [3]
Step 2: Diagnostic Thoracentesis
- Indication: ALL effusions except bilateral effusion strongly suggestive of transudative process (unless atypical or refractory to treatment) [3]
- Send simultaneously with blood sample (for paired protein/LDH ratios)
- Order: biochemistry (protein, LDH, glucose, pH), cell count with differential, microbiology (Gram stain, AFB, culture, TB culture, MTB-PCR), cytology (ideally 20 mL × 3 samples if malignancy suspected) [2]
Step 3: If non-diagnostic
- Pleuroscopy (medical thoracoscopy) / CT-guided percutaneous biopsy [1]
- EBUS-TBNA if mediastinal lymphadenopathy present
- Endobronchial biopsy if endobronchial lesion seen on bronchoscopy
| Scenario | Management |
|---|---|
| Bilateral pleural effusion | Treat underlying cause (e.g. diuretics for heart failure) → chest drain only if failed or respiratory distress [2] |
| Unilateral pleural effusion | Chest drain / therapeutic thoracentesis [2] |
| Malignant pleural effusion | Talc pleurodesis (via chest drain or pleuroscopy), indwelling pleural catheter, systemic treatment of underlying cancer |
| Empyema | Urgent chest drain + IV antibiotics |
| TB pleurisy | Anti-TB treatment |
Signs of pleural effusion [8]:
- Mediastinum shift AWAY (if large)
- Reduced chest wall movement
- Stony dullness on percussion
- Reduced vocal fremitus
- Reduced breath sounds
Additional nuance from senior notes [3]:
- Above the effusion: compressed lung → bronchial breathing + increased vocal resonance (Aegophony — "E to A" change)
- Below/at the effusion: fluid blocks sound → decreased breath sounds + decreased vocal resonance
Past Paper Alert: Signs of Pleural Effusion
The 2024 MCQ EMQ asked: "Stony dull percussion note" → answer is malignant pleural effusion (or any pleural effusion). The key discriminator from consolidation is that consolidation has increased vocal resonance/fremitus while effusion has decreased vocal resonance/fremitus. Both have dullness, but effusion is "stony" dull [9].
Part 2: Lung Cancer — The Diagnosis Behind the Effusion
Non-small cell lung cancer (NSCLC) = 85% of lung cancer [1]
| Feature | Male patients | Female patients (in Hong Kong) |
|---|---|---|
| Smoking | 80% are smokers | < 40% are smokers |
| Histology | Mixed | > 75% adenocarcinoma |
| Risk factors | Smoking, occupational | Environmental: passive smoking, diet, cooking fumes |
| Genetic: EGFR gene mutation — important in non-smoking patients with adenocarcinoma |
Why is this HK-specific data important? In Hong Kong (and East Asia generally), a large proportion of female lung cancer patients are non-smokers with adenocarcinoma harbouring EGFR mutations. This has enormous treatment implications — these patients respond well to EGFR-TKIs (targeted therapy). The lecture explicitly contrasts Eastern vs. Western lung cancer genetics [1].
High Yield: Smoking and Lung Cancer
In Hong Kong: 80% of male lung cancer patients are smokers. Among females, < 40% are smokers, with > 75% having adenocarcinoma. EGFR gene mutations are important in non-smoking adenocarcinoma patients. [1]
WHO classification of lung tumour histology [1]:
I. Malignant Epithelial Tumours (the main ones to know):
| Type | Key Features | Association |
|---|---|---|
| Squamous cell carcinoma (epidermoid) | Central location, cavitation, keratin pearls | Strongest smoking association, ↑Ca²⁺ (PTHrP) |
| Small cell carcinoma (oat cell) | Central, highly aggressive, rapid growth | Strong smoking association, paraneoplastic syndromes (SIADH, Cushing's), treated with chemo ± RT (NOT surgery) |
| Adenocarcinoma | Peripheral location, most common overall, includes bronchioloalveolar pattern | Most common in non-smokers, EGFR mutations, variable histology |
| Large cell carcinoma | Peripheral, undifferentiated, diagnosis of exclusion | Poor prognosis |
| Adenosquamous carcinoma | Mixed features | Uncommon |
| Carcinoid tumour | Neuroendocrine, low-grade | Can cause carcinoid syndrome |
II. Malignant Mesothelial Tumours:
- Malignant mesothelioma — epithelial, fibrous (spindle cell), or biphasic subtypes [1]
- Associated with asbestos exposure (links to GC 083: construction site worker)
Pathogenesis of adenocarcinoma and squamous cell carcinoma differ — the lecture references Wistuba's multistep carcinogenesis model showing that squamous cell carcinoma develops through squamous metaplasia → dysplasia → carcinoma in situ (in proximal airways), while adenocarcinoma arises through atypical adenomatous hyperplasia → adenocarcinoma in situ → invasive adenocarcinoma (in peripheral airways) [1].
2.3 Clinical Features — "Relating Symptoms to Anatomy"
The lecture emphasises that clinical presentation depends on where the tumour is and what structures it invades [1].
| Structure Involved | Symptom/Sign | Explanation |
|---|---|---|
| Bronchus (central) | Cough, haemoptysis, post-obstructive pneumonia | Tumour in airway lumen or compressing it |
| Pleura | Pleuritic chest pain, pleural effusion | Direct invasion or lymphatic obstruction |
| Chest wall / ribs | Chest wall pain | Direct invasion (Pancoast tumour at apex → shoulder/arm pain, Horner's syndrome) |
| Recurrent laryngeal nerve | Hoarseness | Left RLN loops under aortic arch — vulnerable to mediastinal tumours/LNs |
| Phrenic nerve | Elevated hemidiaphragm, dyspnoea | Paralysis of diaphragm |
| SVC | SVC obstruction syndrome (facial swelling, plethora, distended neck veins, arm oedema) | Tumour/LN compressing or invading SVC |
| Oesophagus | Dysphagia | Extrinsic compression |
| Pericardium | Pericardial effusion, tamponade | Direct invasion |
| Sympathetic chain (apex) | Horner's syndrome (ptosis, miosis, anhidrosis, enophthalmos) | Pancoast tumour |
| Brachial plexus (apex) | Arm pain, weakness, wasting (T1 distribution) | Pancoast tumour |
Extra-thoracic manifestation [1]:
- Cachexia
- Clubbing
- Supraclavicular and cervical lymph node enlargement
- Hepatic metastasis (hepatomegaly, deranged liver function)
- Brain metastasis (seizures, change in personality, vomiting)
- Bone metastasis (pathological fractures, hypercalcaemia, bone pain)
- Adrenal metastasis (rarely cortisol insufficiency)
- Spinal cord metastasis (cord compression)
- Skin metastasis
- Choroidal metastasis (impaired visual acuity)
- Unexplained anaemia
Metastasis pattern mnemonic — "Lung Loves Bones, Brain, Liver, Adrenals"
| Syndrome | Tumour Type | Mechanism |
|---|---|---|
| SIADH → hyponatraemia | Small cell | Ectopic ADH production |
| Cushing's syndrome | Small cell | Ectopic ACTH |
| Hypercalcaemia | Squamous cell | PTHrP secretion |
| Lambert-Eaton myasthenic syndrome | Small cell | Anti-VGCC antibodies |
| Hypertrophic pulmonary osteoarthropathy (HPOA) / clubbing | Any, especially adenocarcinoma & squamous cell | Mechanism unclear; involves periosteal new bone formation |
Past Paper 2024 SAQ Q6
A 63-year-old chronic smoker with haemoptysis, weight loss, clubbing, left supraclavicular LN, 3.5 cm lung mass, and sodium of 116 mmol/L. The most likely cause of hyponatraemia is SIADH (ectopic ADH from lung cancer, likely small cell). Investigations: paired serum and urine osmolality, urine sodium. Management: fluid restriction, treat underlying cancer, ± tolvaptan/demeclocycline [10].
Different ways of recognizing lung cancer, different clinical presentation [1]:
- Clinical symptoms and signs
- Clinical syndrome (e.g. paraneoplastic, SVC obstruction)
- Incidental findings on other medical examination (e.g. CT coronary angiogram, CT abdomen)
- Identification of at-risk population — lung cancer screening
The lecture mentions lung cancer screening with low-dose CT (LDCT) in high-risk populations (heavy smokers ≥ 30 pack-years, age 50–80). This is increasingly relevant to exams.
Part 3: Investigations for Suspected Lung Cancer
INVESTIGATIONS [1]:
- To confirm the diagnosis + histological subtypes
- To stage the tumour + assess fitness of patient → to select treatment modality
| Modality | Purpose |
|---|---|
| CXR | First-line; may show mass, effusion, collapse, mediastinal widening |
| CT thorax + upper abdomen | Characterise lesion, assess LN, look for liver/adrenal metastases |
| PET-CT | Excellent tumour imaging. FDG is taken up by cells in glycolysis but is trapped — increased activity in cells with high metabolic rates (tumours and inflammation) [1]. Used for staging: detects distant metastases, helps differentiate benign vs. malignant LN |
PET-CT: Why does it work?
FDG (fluorodeoxyglucose) enters cells via glucose transporters and is phosphorylated but CANNOT continue through glycolysis → it accumulates in metabolically active cells (tumours). This is why cancers "light up" on PET. False positives occur with inflammation/infection (e.g. TB, sarcoidosis). False negatives can occur with low-grade tumours (e.g. carcinoid, some adenocarcinoma in situ). [1]
The lecture outlines multiple modalities for tissue diagnosis [1]:
| Modality | When to Use |
|---|---|
| Sputum cytology | Low sensitivity, rarely sufficient alone |
| Bronchoscopy + endobronchial biopsy | Central lesions visible in the airway |
| Bronchoscopy + transbronchial biopsy | Peripheral lesions accessible through airways |
| CP-EBUS-TBNA (Convex Probe Endobronchial Ultrasound Transbronchial Needle Aspiration) | Mediastinal/hilar lymph node sampling. Sensitivity ~90%. False negative rate ~20%. [1] |
| Radial probe EBUS with guided sheath | Peripheral lung lesions |
| Navigational bronchoscopy | Peripheral lung lesions |
| Image-guided percutaneous biopsy | Peripheral lesions not accessible by bronchoscopy |
| Pleuroscopy | Pleural-based disease, malignant pleural effusion [1] |
| Thoracentesis cytology | Pleural effusion (sensitivity 60–75%) |
| Autofluorescence imaging | Detect early endobronchial neoplasia |
Indications for CP-EBUS-TBNA [1]:
- Staging for lung cancer
- Sampling of mediastinal lymph nodes
- Alternative diagnosis for mediastinal lymphadenopathy (TB, sarcoidosis, lymphoma)
- Tumour mass immediately adjacent to accessible part of the airway
Endobronchial biopsy showed adenocarcinoma [1]:
- CK7 positive
- CK20 negative
- TTF-1 positive
What do these markers mean?
- CK7+/CK20−: Typical of pulmonary adenocarcinoma (CK20+ would suggest GI origin)
- TTF-1 (Thyroid Transcription Factor-1): Expressed in lung and thyroid. TTF-1 positivity in a lung lesion strongly supports primary lung adenocarcinoma rather than metastasis from another site.
Liquid biopsy – to supplement when tissue biopsy is difficult or impossible [1]
| Liquid Biopsy | Tissue Biopsy |
|---|---|
| Relatively non-invasive | Mostly invasive |
| Allows serial monitoring | At diagnosis ± re-biopsy on progression/drug failure |
| Examples: CTC, ctDNA, miRNA, tumour-derived exosomes, oncogenic proteins | Primary tumour histology, metastatic site biopsy |
| Lack of standardised techniques | Well-established/gold-standard |
| Variable sensitivity (tumour cell material leakage dependent) | Sampling representativeness of small biopsy |
Clinical applications of circulating biomarkers [1]:
- For diagnosis
- To guide targeted therapy selection
- To monitor disease progress / treatment response
- To identify new targets
- Early detection of disease recurrence
- For prognostication
Gold-standard for diagnosis is still lung cancer tissue for histological diagnosis [1]
Key point: Liquid biopsy is especially useful for detecting EGFR T790M resistance mutation when a patient on first-line EGFR-TKI progresses — you can test plasma ctDNA instead of re-biopsy.
Staging for NSCLC based on TNM Staging Classification (Updated 8th ed. TNM staging manual in 2018) [1]:
| Component | What It Assesses |
|---|---|
| T — Tumour | Size and local invasion |
| N — Nodes | Hilar, mediastinal or extra-thoracic; ipsilateral vs. contralateral |
| M — Metastasis | Distant spread |
| Stage | Extent | Operability |
|---|---|---|
| I | Early disease | OPERABLE — Surgery (if medically fit) |
| II | Early disease | OPERABLE — Surgery |
| III | Locally advanced | RT + CT (chemoradiation) |
| IV | Advanced / metastatic | CT (chemotherapy) / targeted therapy / immunotherapy |
Stage I & II = OPERABLE → SURGERY Stage III = INOPERABLE → RT + CT Stage IV = INOPERABLE → CT (if good performance status) [1]
Why does operability matter? Surgical resection is the only curative treatment for NSCLC. Once the tumour has spread to contralateral mediastinal nodes (N3) or distant sites (M1), surgery cannot remove all disease, and systemic treatment is needed.
Part 5: Treatment of Lung Cancer
Treatment for lung cancer [1]:
| NSCLC | SCLC | |
|---|---|---|
| Early stage | Resection | — |
| Locally advanced | Chemo ± RT ± resection | Limited stage: Chemo ± RT |
| Advanced | Chemotherapy or targeted therapy or immunotherapy | Extensive stage: Chemo |
| Relapse | Tests for targets → further options | Tests for targets |
Cyclical combination chemotherapy [1]: A platinum drug (e.g. cisplatin or carboplatin) + a newer generation cytotoxic drug (e.g. pemetrexed, taxol, gemcitabine) Response rate about 30–40% Note side effects especially myelosuppression
Workup for lung cancer systemic treatment [1]:
- Check hepatitis B carrier status — if HBV carrier, cover with antiviral prophylaxis (e.g. entecavir) throughout chemotherapy
- Pre-medications for some regimens: e.g. Vitamin B12 and folic acid supplementation before pemetrexed chemotherapy
Why HBV status matters: Chemotherapy-induced immunosuppression can reactivate dormant hepatitis B, causing fulminant hepatitis. This is extremely high-yield in Hong Kong where HBV prevalence is high.
Exam Pearl: HBV Reactivation Prevention
ALWAYS check HBsAg (and anti-HBc) before starting cytotoxic chemotherapy or immunosuppression. If HBsAg positive, start antiviral prophylaxis (entecavir preferred) BEFORE chemotherapy and continue throughout + 6–12 months after. [1]
5.4 Molecular Targeted Therapy
Molecular Targeted Therapy — Indications: As primary treatment for tumour with oncogenic molecular targets [1]
Biomarkers: Sensitising EGFR mutations [1]:
- 15-nucleotide deletion in exon 19 (del19)
- L858R or L861Q in exon 21
Resistant mutation: T790M in exon 20
(Mutations detectable in tumours or plasma DNA)
Clinical indications [1]:
- Sensitising EGFR mutations → Gefitinib / Erlotinib / Afatinib (1st/2nd gen TKIs)
- Resistant EGFR mutations (T790M) → Osimertinib (3rd gen TKI)
- Osimertinib is now preferred first-line for sensitising mutations as well
Common adverse effects from EGFR-TKI [1]:
- Skin rash (acneiform)
- Stomatitis/mucositis (WHO Grade III = can only tolerate fluid diet)
- Paronychia with ingrown toenail
- Diarrhoea
- Interstitial lung disease (rare but serious)
Biomarkers: ALK immunohistochemical staining or ALK FISH [1]
Clinical indications: ALK re-arranged or IHC +ve tumour
- First line: Crizotinib (or now Alectinib preferred)
- Second line or beyond: Ceritinib / Alectinib / Brigatinib / Lorlatinib or systemic chemo/immunotherapy
The lecture slide on advanced NSCLC with actionable mutations [1] lists:
| Target | Drug(s) |
|---|---|
| EGFR mutation | Osimertinib (preferred), erlotinib, afatinib, gefitinib, dacomitinib |
| ALK translocation | Alectinib (preferred), brigatinib, ceritinib, lorlatinib, crizotinib |
| ROS1 rearrangement | Crizotinib or entrectinib |
| BRAF V600E mutation | Dabrafenib + trametinib |
| NTRK positive | Entrectinib or larotrectinib |
| RET positive | Selpercatinib or pralsetinib |
| METex14 positive | Capmatinib or tepotinib |
Anti-PDL1 therapy [1]: Biomarker: PDL1 immunohistochemical staining intensity — Tumour Proportional Score (TPS)
- TPS > 50% predicts better response to anti-PDL1 therapy
Clinical indications [1]:
- 1st line: anti-PDL1 therapy combined with chemotherapy in tumours with PDL1 expression
- 2nd line or beyond: anti-PDL1 therapy alone (no need for PDL1 test)
Why immunotherapy works: PD-L1 on tumour cells binds PD-1 on T cells, sending an "off" signal that prevents the immune system from attacking the cancer. Anti-PD-L1/PD-1 antibodies (e.g. pembrolizumab, nivolumab, atezolizumab) block this interaction, "releasing the brakes" on the immune system.
| Stage | Treatment |
|---|---|
| Limited stage | Chemo ± RT |
| Extensive stage | Chemo |
SCLC is NOT treated with surgery (it is already disseminated at diagnosis in most cases). It is exquisitely sensitive to chemotherapy initially but almost always relapses.
Summary [1]:
- Variable clinical presentation of lung cancer, from asymptomatic to frank systemic disturbance or clinical syndromes
- Different diagnostic methods to suit individual presentation
- The aims of diagnostic investigation should be:
- Distinction between benign and malignant lesion
- To obtain tissue diagnosis, especially for at-risk population
- To work up for staging with diagnosis of lung cancer and to evaluate for metastasis
- Functional assessment for patients in preparation for treatment modalities
Past Paper Themes
| Paper | Question | Key Point |
|---|---|---|
| 2020 MCQ Q6 [11] | Exudative effusion criteria — which finding is compatible? | Pleural fluid protein / serum protein ratio = 0.55 → > 0.5 = EXUDATIVE. The other options (neutrophil ratio, pH ratio, LDH ratio of 0.55) don't meet criteria or are not part of Light's criteria. |
| 2022 MCQ Q36 [12] | Man on infliximab (anti-TNF) with pleural effusion → most useful early diagnostic test? | Pleural biopsy (anti-TNF → TB risk → pleural TB; pleural fluid culture only positive in ~1/3; ADA useful but biopsy gives histology + culture) |
| 2022 SAQ Q2 [13] | 45-year-old male smoker with massive right pleural effusion → respiratory symptoms, systemic symptoms, physical signs | Respiratory Sx: cough, haemoptysis, chest pain, SOB. Systemic Sx: weight loss, fever/night sweats. Signs: stony dullness, reduced breath sounds, reduced VF, tracheal deviation |
| 2021 Minicase Case 3 [14] | 56-year-old woman with lung mass + right pleural effusion | Most serious condition: lung cancer with malignant pleural effusion. Ix to confirm: CT thorax, bronchoscopy + biopsy, pleural fluid cytology, PET-CT |
| 2024 SAQ Q6 [10] | Chronic smoker, haemoptysis, Na 116 → SIADH from lung cancer | Confirm with paired serum/urine osmolality, urine Na |
| 2024 MCQ EMQ [9] | Stony dull percussion note → malignant pleural effusion | Key discriminator from consolidation |
-
MCQ: A 64-year-old chronic smoker has a right-sided pleural effusion. Thoracentesis shows pleural fluid protein/serum protein = 0.6, LDH ratio = 0.7, lymphocyte-predominant. What is the most likely diagnosis?
- Markscheme: Malignant pleural effusion (exudative by Light's criteria, lymphocyte-predominant in chronic causes including malignancy)
-
SAQ: List four causes of exudative pleural effusion.
- Malignancy, TB, parapneumonic effusion/empyema, pulmonary embolism, connective tissue disease (RA/SLE)
-
SAQ: A lung biopsy shows CK7+, CK20−, TTF-1+. What is the diagnosis?
- Primary lung adenocarcinoma
-
MCQ: Which molecular test is most important to perform before starting systemic treatment in a non-smoking female with advanced lung adenocarcinoma?
- EGFR mutation testing
-
SAQ: Name three extrathoracic manifestations of lung cancer.
- Brain metastasis, bone metastasis, hepatic metastasis, supraclavicular lymphadenopathy, adrenal metastasis, skin metastasis, clubbing, cachexia
-
MCQ: What antiviral prophylaxis should be given to an HBsAg-positive patient starting chemotherapy for lung cancer?
- Entecavir
-
SAQ: Describe the principles of investigation for suspected lung cancer.
- (1) Confirm diagnosis + histological subtype; (2) Stage the tumour + assess fitness to select treatment
-
MCQ: PET-CT shows increased FDG uptake. This is because:
- FDG enters cells via glucose transporters and is phosphorylated but cannot continue through glycolysis → accumulates in metabolically active cells
High Yield Summary
Pleural Effusion: Apply Light's criteria (protein ratio > 0.5, LDH ratio > 0.6, fluid LDH > 2/3 ULN serum LDH) → exudate. In a chronic smoker: think malignancy. Lymphocyte-predominant = chronic process (malignancy, TB). Cytology sensitivity ~60–75%. If non-diagnostic → pleuroscopy/EBUS-TBNA.
Lung Cancer: NSCLC = 85%. Adenocarcinoma is the most common subtype, especially in HK women (often non-smokers with EGFR mutations). CK7+/CK20−/TTF-1+ = primary lung adenocarcinoma. Stage I–II: surgery. Stage III: chemoradiation. Stage IV: molecular testing first → EGFR-TKI (osimertinib) for EGFR-mutant, ALK-TKI (alectinib) for ALK+, chemo ± immunotherapy (anti-PD-L1) for wild-type. Always check HBV status before chemotherapy. Liquid biopsy supplements tissue biopsy for molecular targets.
Key Exam Discriminators: Stony dull = effusion (not consolidation). Decreased VR/VF = effusion; Increased VR/VF = consolidation. Light's criteria overdiagnose exudates in diuretic patients. PET false positive in infection/inflammation.
Active Recall - Pleural Effusion and Lung Cancer
[1] Lecture slides: GC 077. Pleural effusion in a chronic smoker.pdf (all pages) [2] Senior notes: Maksim Medicine Notes.pdf (p292) [3] Senior notes: Ryan Ho Fundamentals.pdf (p228) [4] Senior notes: Block A - Renal Replacement Therapies.pdf (p17) [5] Senior notes: Gen Clerk Anaes + Microbiology Summary.pdf (p33) [6] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p274) [7] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (p468) [8] Lecture slides: Respiratory Examination for CFB_James Ho_2024.pdf (p52) [9] Past papers: 2024 Fourth Summative MCQ.pdf (p37, EMQ Q1-4) [10] Past papers: 2024 Fourth Summative SAQ.pdf (p7, Q6) [11] Past papers: 2020 Fourth Summative Assessment MCQ paper.pdf (p3, Q6) [12] Past papers: 2022 Fourth Summative MCQ.pdf (p14, Q36) [13] Past papers: 2022 Fourth Summative SAQ.pdf (p3, Q2) [14] Past papers: 2021 Fourth Summative Minicase.pdf (p24, Case 3)
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GC078 Polyuria And Polydipsia Glucose Metabolism, Diabetes Mellitus, Diabetic Ketoacidosis
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