Pathology · Year 2 · from Pathology
Case 2: Small Cell Lung Cancer with SIADH and Paraneoplastic Syndrome
Patient Demographics
- Age: 67 years old
- Sex: Male
- Occupation: Former construction worker
Chief Complaint
"Cough, weakness, and confusion for 3 weeks"
History of Present Illness
A 67-year-old male with a 50 pack-year smoking history presents with a 3-week history of productive cough, progressive weakness, and confusion. His family reports he has been increasingly disoriented and has fallen twice at home. He has lost 7 kg over the past 2 months. He initially attributed symptoms to a respiratory infection but has worsened despite antibiotics. He also notes difficulty rising from a chair and climbing stairs.
Physical Examination
- Vital Signs: BP 136/82 mmHg, HR 78 bpm, RR 20/min, Temp 37.0C, SpO2 94% on room air
- General: Thin male, appears confused, no acute distress
- HEENT: Moist mucous membranes, no signs of dehydration
- Respiratory: Decreased breath sounds in right upper lobe, no wheezing
- Neurologic: Oriented to person only, proximal muscle weakness (4/5 in shoulders and hips), strength improves slightly with repeated testing, deep tendon reflexes diminished
- No edema
Diagnostic Workup
Laboratory Studies:
| Test | Result | Reference Range |
|---|---|---|
| Sodium | 118 mEq/L | 136-145 mEq/L |
| Serum osmolality | 248 mOsm/kg | 280-300 mOsm/kg |
| Urine osmolality | 520 mOsm/kg | 50-1200 mOsm/kg |
| Urine sodium | 85 mEq/L | Variable |
| TSH | 2.1 mU/L | 0.5-5.0 mU/L |
| Cortisol (AM) | 18 mcg/dL | 5-25 mcg/dL |
Imaging:
- Chest X-ray: Large right hilar mass with mediastinal widening
- CT Chest: 6 cm right hilar mass encasing right mainstem bronchus, extensive mediastinal lymphadenopathy, small bilateral pleural effusions
- MRI Brain: Multiple small enhancing lesions consistent with metastases
Bronchoscopy with Biopsy:
- Endobronchial tumor obstructing right upper lobe bronchus
- Pathology: Small cell carcinoma, positive for synaptophysin, chromogranin, CD56
Electrophysiology:
- EMG showing incremental response to repetitive nerve stimulation (characteristic of Lambert-Eaton)
Antibody Testing:
- Anti-voltage-gated calcium channel (VGCC) antibodies: Positive
Pathology Correlation
This case demonstrates multiple paraneoplastic syndromes associated with small cell lung cancer:
1. SIADH (Syndrome of Inappropriate ADH Secretion):
- Ectopic production of ADH (vasopressin) by tumor cells
- Causes water retention and dilutional hyponatremia
- Key features: Euvolemia, low serum osmolality, inappropriately concentrated urine
- Must exclude other causes of hyponatremia
2. Lambert-Eaton Myasthenic Syndrome (LEMS):
- Antibodies against voltage-gated calcium channels (VGCCs)
- Antibodies produced against tumor antigens cross-react with nerve terminals
- Causes impaired acetylcholine release at neuromuscular junction
- Key features: Proximal weakness, autonomic dysfunction, improvement with repeated activity (unlike myasthenia gravis)
Small Cell Carcinoma Characteristics:
- Neuroendocrine tumor (positive for synaptophysin, chromogranin)
- Highly aggressive, early metastasis
- Strong association with smoking
- Most common to produce paraneoplastic syndromes
- Staging: Limited vs. Extensive disease
Other SCLC Paraneoplastic Syndromes:
- Ectopic ACTH (Cushing syndrome)
- Anti-Hu antibodies (limbic encephalitis, sensory neuropathy)
- Cerebellar degeneration
Clinical Image
Histopathology of small cell lung carcinoma showing sheets of small cells with scant cytoplasm, hyperchromatic nuclei with finely granular "salt and pepper" chromatin, nuclear molding, and frequent mitotic figures. Neuroendocrine markers are typically positive.
Image Source: Wikimedia Commons - "Small cell lung cancer" License: CC BY-SA 3.0 URL: https://commons.wikimedia.org/wiki/File:Small_cell_lung_cancer_-_cytology.jpg
Diagnosis
- Extensive-Stage Small Cell Lung Cancer (brain metastases)
- SIADH (paraneoplastic)
- Lambert-Eaton Myasthenic Syndrome (paraneoplastic)
Treatment
SIADH Management:
- Fluid restriction (500-1000 mL/day)
- Salt tablets if tolerated
- Consider tolvaptan (vasopressin receptor antagonist) if severe
- Treat underlying cancer
LEMS Management:
- Treat underlying cancer (primary therapy)
- 3,4-diaminopyridine to enhance acetylcholine release
- Pyridostigmine as adjunct
- IVIG or plasmapheresis if severe
Oncologic Treatment:
- Chemotherapy (platinum-etoposide) with immunotherapy
- Prophylactic cranial irradiation (if response to chemotherapy)
- Whole brain radiation for brain metastases
- Palliative care integration
Teaching Points
- Small cell lung cancer is the tumor most frequently associated with paraneoplastic syndromes
- SIADH causes euvolemic hyponatremia with inappropriately concentrated urine
- Lambert-Eaton syndrome features proximal weakness that improves with activity (presynaptic NMJ disorder)
- Paraneoplastic syndromes may precede cancer diagnosis and resolve with successful treatment
- Recognition of paraneoplastic syndromes should prompt thorough malignancy workup
- Cancer screening (low-dose CT for lung cancer) can detect cancers at earlier, more treatable stages