Respiratory · Year 1 · from Respiratory
Case 2: Small Cell Lung Cancer - Paraneoplastic Syndrome
Clinical Image
Source: Wikimedia Commons - Small cell lung cancer - CC BY-SA 3.0
Patient Presentation
A 64-year-old man with a 60-pack-year smoking history presents with progressive weakness, difficulty rising from a chair, and dry mouth for 6 weeks. He also reports mild weight loss and a cough productive of blood-tinged sputum. His wife notes that his handgrip seems to improve after he has been using his hands for a while.
Demographics
- Age: 64 years
- Sex: Male
- Past Medical History: COPD, hypertension
- Medications: Tiotropium, albuterol inhaler, lisinopril
- Social History: 60 pack-year smoking history, quit 2 years ago
Chief Complaint
Progressive weakness, hemoptysis, and weight loss
Physical Examination
- Blood pressure: 148/92 mmHg
- Heart rate: 98 bpm
- Weight: 72 kg (down 5 kg in 2 months)
- General: Cachectic, appears ill
- Respiratory: Decreased breath sounds left upper lobe
- Neurological:
- Proximal muscle weakness (3/5 hip flexion, 4-/5 shoulder abduction)
- Hyporeflexia at rest, facilitation after brief exercise
- Dry mouth
- No ptosis or diplopia
Workup
- Chest X-ray: Large left hilar mass with mediastinal widening
- CT chest: 5.5 cm left hilar mass with extensive mediastinal lymphadenopathy, left pleural effusion
- PET-CT: FDG-avid primary, mediastinal nodes, left adrenal metastasis
- Brain MRI: No brain metastases
- Bronchoscopy with biopsy: Small cell lung cancer (small cells with scant cytoplasm, high mitotic rate, neuroendocrine markers positive)
- Staging: Extensive stage SCLC
- Paraneoplastic workup:
- Anti-VGCC antibodies: Positive (Lambert-Eaton Myasthenic Syndrome)
- Serum sodium: 124 mEq/L (low)
- Urine osmolality: 520 mOsm/kg (inappropriately concentrated - SIADH)
Diagnosis
- Extensive Stage Small Cell Lung Cancer
- Lambert-Eaton Myasthenic Syndrome (paraneoplastic)
- SIADH (paraneoplastic hyponatremia)
Treatment
- Chemotherapy + Immunotherapy:
- Platinum (carboplatin) + etoposide + durvalumab or atezolizumab
- First-line standard for extensive stage SCLC
- Fluid restriction for SIADH
- Treatment of underlying cancer often improves LEMS
- Symptomatic LEMS treatment: 3,4-diaminopyridine (amifampridine)
- Prophylactic cranial irradiation (PCI) if good response to treatment
- Surveillance for brain metastases
- Smoking cessation support (though already quit)
Physiological Principles Demonstrated
- SCLC neuroendocrine features: SCLC arises from neuroendocrine cells, explaining its propensity for paraneoplastic syndromes through ectopic hormone production (SIADH, Cushing) and autoimmune phenomena (LEMS, cerebellar degeneration).
- Lambert-Eaton mechanism: Antibodies against voltage-gated calcium channels (VGCC) at presynaptic motor nerve terminals reduce acetylcholine release. Unlike myasthenia gravis, repeated stimulation allows calcium accumulation and improved strength (facilitation).
- SIADH mechanism: Ectopic ADH secretion causes water retention and dilutional hyponatremia with inappropriately concentrated urine.
- Chemo-responsive but poor prognosis: SCLC is initially very responsive to chemotherapy (high proliferative fraction), but rapid relapse is common, and 5-year survival for extensive stage is <10%.