Pleural Disease — Clinical Case

DCE Long Case

Patient brief (provided to trainee)

Patient: Mr Robert Wilson, 68 years old. [1]

Presenting complaint: Six-week history of progressive exertional dyspnoea, persistent right chest wall pain, and 8 kg unintentional weight loss. [1]

Past history:

• COPD diagnosed 10 years ago — FEV1 60% predicted (GOLD 3). Still smoking 20 cigarettes/day (50 pack-year total)
• Hypertension, well controlled
• No known malignancy [1]

Occupational history:

• Shipyard worker and welder from 1972 to 1988 — 16 years of documented heavy asbestos exposure (lagging pipes, insulation removal, demolition)
• Later worked as a maintenance fitter until retirement at 65
• No known secondary exposure [1]

Current medications:

• Tiotropium 18 mcg inhaled daily
• Salbutamol inhaler PRN
• Amlodipine 5 mg daily [1]

Examination findings (trainee elicits):

• Cachectic, in mild respiratory distress at rest
• Respiratory rate 24/min, SpO2 92% on room air
• Blood pressure 128/76, heart rate 96, temperature 36.8
• Reduced chest wall expansion on the right
• Stony dullness to percussion over the lower two-thirds of the right hemithorax
• Absent breath sounds over the right lower and middle zones
• Reduced vocal resonance and tactile vocal fremitus on the right
• Egophony (e-to-a change) at the upper border of the dullness
• Left lung clear
• No lymphadenopathy, no finger clubbing, no signs of heart failure [1]

Investigations:

• WBC 9.2, CRP 42 (mildly elevated), normal renal and hepatic function
• CXR: large right pleural effusion with partial volume loss of the right hemithorax
• CT chest with contrast: circumferential right pleural thickening with a nodular rind encasing the right lung, a large right pleural effusion, calcified pleural plaques bilaterally, no distant metastases, no mediastinal lymphadenopathy
• Pleural fluid (diagnostic tap): exudate by Light's criteria (protein 48 g/L, LDH 520 U/L), lymphocytic predominance, cytology negative on two samples, pH 7.32, glucose 3.8 [1]

Candidate's structured presentation (model)

Opening statement: [1]

"Mr Wilson is a 68-year-old former shipyard worker with 16 years of heavy asbestos exposure who presents with a 6-week history of progressive dyspnoea, right chest wall pain, and 8 kg of weight loss. He has COPD (GOLD 3) and is a 50 pack-year smoker. [1]

On examination he is cachectic and breathless at rest, with stony dullness, absent breath sounds, and reduced vocal resonance over the lower two-thirds of the right hemithorax. His CT chest shows circumferential right pleural thickening with a nodular rind, a large right pleural effusion, and bilateral calcified pleural plaques consistent with asbestos exposure. Pleural fluid is an exudate with lymphocytic predominance and negative cytology. [1]

The clinical and radiological picture is highly suggestive of malignant pleural mesothelioma. Cytology was negative on two samples, which is common in mesothelioma (cytology sensitivity is only 30-50%), so histological confirmation is required. [1]

His main problems are:

1. Probable malignant pleural mesothelioma — needs histological confirmation
2. A large symptomatic right pleural effusion requiring drainage and definitive pleural control
3. Severe chest wall pain from pleural and chest wall involvement
4. Cachexia and nutritional decline
5. Asbestos exposure requiring compensation documentation and referral
6. COPD management and smoking cessation" [1]

Management plan: [1]

1. Confirm the diagnosis (immediate):

   • Medical thoracoscopy (local anaesthetic, semi-rigid) for direct visualisation, targeted biopsy, fluid drainage, and talc poudrage pleurodesis in a single procedure — OR a CT-guided cutting-needle biopsy with immunohistochemistry if thoracoscopy is not available
   • Immunohistochemistry panel: mesothelioma markers (calretinin, WT-1, D2-40, CK5/6) versus adenocarcinoma markers (TTF-1, CEA, Ber-EP4)
   • Serum mesothelin as a supportive biomarker [1]

2. Establish definitive pleural control:

   • At thoracoscopy, drain the effusion and assess lung re-expansion
   • If the lung re-expands: talc poudrage pleurodesis at the same procedure
   • If the lung is trapped: insert an indwelling pleural catheter (PleurX) for outpatient drainage — the TIME2 trial (Davies, JAMA 2012) showed equivalent dyspnoea relief with IPC versus talc pleurodesis [2]

3. Plan chemotherapy:

   • Refer to the medical oncology MDT
   • If ECOG performance status 0-1: pemetrexed plus cisplatin every 21 days for up to 6 cycles, with folic acid and vitamin B12 supplementation — the Vogelzang trial (JCO 2003) showed median survival improved from 9.3 to 12.1 months [1]
   • If borderline fitness: substitute carboplatin for cisplatin

4. Manage pain:

   • Multimodal analgesia with the palliative care and pain teams: long-acting opioid (oral morphine or transdermal fentanyl), gabapentinoid for neuropathic component, intercostal nerve block if localised, palliative radiotherapy for chest wall disease [1]

5. Address compensation:

   • Meticulously document the occupational asbestos exposure
   • Refer to icare Dust Diseases Care (or equivalent state scheme) for lump sum and medical compensation
   • Advise on common-law compensation and refer to a specialist asbestos lawyer [1]

6. Holistic and supportive care:

   • Palliative care involvement for symptom control and advance care planning
   • Nutritional support (dietitian, oral supplements)
   • Smoking cessation counselling
   • Honest discussion of prognosis (median survival 8-12 months; epithelioid subtype fares best)
   • Family support and counselling [1]

Examiner discussion questions

Q: "His pleural fluid was an exudate by Light's criteria. Walk me through the criteria." [1]

"Light's criteria classify an effusion as an exudate if any one of three conditions is met: the pleural fluid to serum protein ratio is over 0.5, the pleural fluid to serum LDH ratio is over 0.6, or the pleural fluid LDH is over two-thirds the upper limit of normal for serum LDH. If none is met, it is a transudate. The criteria are highly sensitive — approximately 98% — meaning very few exudates are missed, but they misclassify approximately 25% of heart failure transudates as exudates, especially after diuretic therapy. In this case, the protein of 48 g/L and LDH of 520 U/L clearly meet the exudate criteria, which is consistent with a malignant or inflammatory cause. The lymphocytic predominance further supports malignancy or tuberculosis. Light's original study was published in Annals of Internal Medicine in 1972 and remains the standard over 50 years later." [3]

Q: "Cytology was negative twice. How do you explain that, and what is the sensitivity of cytology in mesothelioma?" [1]

"Pleural fluid cytology is positive in only approximately 30 to 50% of mesothelioma, which is lower than for metastatic adenocarcinoma involving the pleura (where it is approximately 50 to 60%, rising to 80% with repeat taps). The lower yield in mesothelioma is because the tumour grows as a sheet along the pleural surface rather than shedding cells freely into the fluid. A negative cytology does not exclude mesothelioma, and the diagnosis requires histological confirmation by pleural biopsy. Medical thoracoscopy has a diagnostic sensitivity of over 90% because it allows direct visualisation and targeted biopsy of nodular areas. CT-guided cutting-needle biopsy is an alternative with a sensitivity of approximately 85 to 90% for malignancy." [1]

Q: "How would you distinguish mesothelioma from metastatic adenocarcinoma histologically?" [1]

"By immunohistochemistry. Mesothelioma is positive for mesothelial markers — calretinin, WT-1, D2-40 (podoplanin), and CK5/6 — and negative for epithelial markers such as TTF-1 (thyroid transcription factor-1, which marks lung and thyroid adenocarcinoma), CEA (carcinoembryonic antigen), Ber-EP4, and claudin-4. Metastatic adenocarcinoma shows the opposite pattern — positive for TTF-1 if it is a lung primary, CEA, Ber-EP4, and claudin-4, and negative for the mesothelial markers. No single marker is diagnostic, so a panel of at least two mesothelial and two epithelial markers is used. The histological subtype of mesothelioma also matters for prognosis — epithelioid carries the best prognosis (median 12-20 months), sarcomatoid the worst (4-8 months), and biphasic is intermediate." [1]

Q: "He asks whether surgery can cure him. What do you say?" [1]

"I would be honest that surgery is not curative and is not standard of care for mesothelioma outside specialist centres and clinical trials. The two radical surgical procedures — extrapleural pneumonectomy (EPP) and pleurectomy with decortication (P/D) — are major operations with significant morbidity and mortality. The UK MARS trial, which randomised patients to EPP versus no EPP, was stopped early because of excess mortality in the surgery arm and concluded that EPP should not be offered as standard treatment. Some highly selected, fit patients with resectable epithelioid disease may be offered limited surgery as part of multimodality therapy at specialist centres, but this is investigational. Given his COPD and 50 pack-year smoking history, he would not be a candidate for radical surgery in any case. The focus is on chemotherapy for disease-modifying benefit and symptom control." [1]

Q: "What is his prognosis?" [1]

"Median survival for mesothelioma is 8 to 12 months from diagnosis, though this varies by histological subtype and performance status. The epithelioid subtype — which is the most common and carries the best prognosis — has a median survival of 12 to 20 months. The sarcomatoid subtype has a median of only 4 to 8 months, and the biphasic subtype is intermediate. Good performance status, earlier stage, and epithelioid histology are favourable factors. Chemotherapy with pemetrexed and cisplatin provides a modest survival benefit of approximately 3 months on average and improves symptoms. I would discuss this honestly but compassionally with him and his family, framing the prognosis in terms of months rather than years, and emphasising that the goal is quality of life and symptom control alongside disease-modifying treatment." [1]

DCE Short Case — Respiratory Examination in Pleural Effusion

Instruction

"Examine this patient's respiratory system. He was admitted with a pleural effusion and is now recovering on the ward. You have 7 minutes for examination and 8 minutes for discussion." [1]

Key signs the patient demonstrates

• Reduced chest expansion on the affected side (resolving as the effusion drains)
• Stony dull percussion note over the residual effusion
• Reduced or absent breath sounds over the affected area
• Reduced vocal resonance and tactile vocal fremitus — the fluid blocks sound transmission
• Egophony (e-to-a change) at the upper border of the effusion (compressed lung)
• Possible pleural rub if there is pleural inflammation [1]

Presentation template

"I examined Mr Wilson's respiratory system. He is comfortable at rest but appears breathless on mild exertion. He is not cyanosed or clubbed. The respiratory rate is 22 per minute. [1]

The trachea is central. Chest wall expansion is reduced on the right side. On percussion, there is stony dullness over the right middle and lower zones. Tactile vocal fremitus is reduced over this area. On auscultation, breath sounds are reduced over the right lower zone, with reduced vocal resonance. At the upper border of the dullness there is an egophonic e-to-a change. There is no wheeze. The left lung is clear. [1]

In summary, these findings are consistent with a right pleural effusion, consistent with the working diagnosis of mesothelioma." [1]

Discussion template

1. Summarise findings — "right pleural effusion, likely malignant given the history of asbestos exposure." [1]

2. Distinguish from consolidation — "The key discriminator from consolidation is the pattern of sound transmission. Both effusion and consolidation produce dullness, but in effusion the fluid blocks sound transmission, producing reduced breath sounds and reduced vocal resonance. In consolidation, the solidified lung conducts sound better, producing bronchial breathing and increased vocal resonance with whispered pectoriloquy." [1]

3. Investigation pathway — "I would arrange a CT chest with contrast to characterise the pleura, a diagnostic thoracentesis with fluid analysis (protein, LDH, pH, glucose, cell count, cytology, culture), and pleural biopsy if cytology is negative." [1]

4. Management of the effusion — "Drain for symptom relief (limit 1.5 L), assess lung re-expansion, and proceed to pleurodesis if the lung re-expands or an indwelling catheter if the lung is trapped." [1]

Examiner: "What is the significance of the calcified pleural plaques on his CT?" [1]

"Pleural plaques are benign areas of localised parietal pleural fibrosis caused by asbestos exposure. They are the most common radiological manifestation of asbestos exposure and are typically calcified, found along the lower chest wall and diaphragm, sparing the costophrenic angles and visceral pleura. Plaques are not premalignant — they do not transform into mesothelioma — but their presence confirms significant asbestos exposure, which puts the patient at risk of mesothelioma, asbestosis, and benign asbestos-related pleural effusion. In this patient, the plaques confirm the exposure history and, combined with the pleural thickening, rind, and effusion, strongly support the diagnosis of mesothelioma. Plaques also have medicolegal significance — their presence documents asbestos exposure for compensation purposes." [1]