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A 64-year-old male heavy smoker (50 pack-years) presents to the outpatient clinic with a 6-week history of progressive cough, intermittent blood-streaked sputum, 8 kg unintentional weight loss, and right-sided chest pain. On examination he is cachectic, has digital clubbing, a hard left supraclavicular lymph node, and dullness with reduced breath sounds at the right base. Chest X-ray shows a 6 cm cavitating right lower-lobe mass with mediastinal widening. Serum calcium is 3.1 mmol/L (normal 2.2 to 2.6), with normal PTH.
Questions
a) What is the most likely diagnosis and the histological subtype? Give three reasons. (2 marks)
Likely squamous cell carcinoma of the lung (bronchogenic carcinoma). Reasons: (1) central/cavitating hilar/lower-lobe mass in a heavy smoker; (2) PTHrP-mediated hypercalcaemia is classical for squamous cell carcinoma; (3) digital clubbing/HPOA is most often associated with NSCLC (squamous and large cell).
b) Outline the investigations you would order to confirm the diagnosis and stage the disease. (3 marks)
- Contrast-enhanced CT chest + abdomen/pelvis to characterise the mass and assess mediastinal nodes, liver, adrenal, bone involvement.
- Tissue diagnosis: bronchoscopy with biopsy (central lesion) ± EBUS-TBNA of mediastinal nodes; FNA of the supraclavicular node is the least invasive route to histology.
- Histology with immunohistochemistry (p40/p63 positive for squamous; TTF-1 for adenocarcinoma) and molecular testing (EGFR, ALK, ROS1, PD-L1) — though squamous less often driver-mutant.
- PET-CT for nodal and distant metastatic staging.
- MRI brain (stage III/IV, symptomatic) and PFTs if curative-intent therapy planned.
- Treat the hypercalcaemia: IV saline + IV zoledronic acid 4 mg.
c) Describe the stage-based definitive management of non-small cell lung cancer. (3 marks)
- Stage I to II (early, operable) — surgical resection (lobectomy + mediastinal node dissection, VATS) ± adjuvant cisplatin-based chemotherapy (stage II to IIIA); SBRT if medically inoperable.
- Stage III (unresectable, locally advanced) — concurrent chemoradiotherapy (platinum doublet + thoracic RT) followed by consolidation durvalumab (PACIFIC).
- Stage IV (advanced) — guided by molecular profile: EGFR → osimertinib (FLAURA); ALK → alectinib; PD-L1 TPS at least 50% → pembrolizumab monotherapy (KEYNOTE-024); no driver → platinum doublet + immunotherapy (e.g., carboplatin + paclitaxel + atezolizumab ± bevacizumab, IMpower150). Palliative radiotherapy to symptomatic sites.
d) List four complications of lung cancer and two oncological emergencies. (2 marks)
Complications: brain/bone/liver/adrenal metastases; post-obstructive pneumonia; pleural effusion; recurrent laryngeal/phrenic nerve palsy; paraneoplastic syndromes (SIADH, hypercalcaemia, Lambert-Eaton, HPOA); pathological fracture; thromboembolism. Oncological emergencies: superior vena cava obstruction, spinal cord compression, hypercalcaemic crisis, massive haemoptysis, raised intracranial pressure from brain metastases.