# Clinical Cases: Lung Cancer

## Case 1: Non-Small Cell Lung Cancer - Adenocarcinoma with EGFR Mutation

### Clinical Image
![Lung Cancer CT](case_01_image.jpg)
*Source: [Wikimedia Commons - Lung cancer CT](https://commons.wikimedia.org/wiki/File:Lung_cancer_in_right_lung.jpg) - CC BY-SA 3.0*

### Patient Presentation
A 58-year-old Asian woman, never-smoker, presents with a 2-month history of persistent dry cough and mild exertional dyspnea. She has no hemoptysis, fever, or weight loss. She initially thought it was allergies but the cough has not improved with antihistamines. A chest X-ray ordered by her primary care physician revealed a right lung mass.

### Demographics
- Age: 58 years
- Sex: Female
- Past Medical History: Hypothyroidism
- Medications: Levothyroxine
- Social History: Never smoker, works as an accountant
- Family History: No lung cancer

### Chief Complaint
Persistent cough and mild dyspnea for 2 months

### Physical Examination
- Blood pressure: 128/76 mmHg
- Heart rate: 78 bpm
- Respiratory rate: 16/min
- Oxygen saturation: 97% on room air
- General: Well-appearing, no distress
- Respiratory: Decreased breath sounds at right base, no wheezing
- Lymph nodes: No palpable cervical or supraclavicular adenopathy
- Neurological: Normal

### Workup
- Chest X-ray: 4 cm right lower lobe mass
- CT chest with contrast: 4.2 cm spiculated mass in right lower lobe with ipsilateral hilar lymphadenopathy (N1)
- PET-CT: FDG-avid primary mass and hilar nodes; no distant metastases
- Brain MRI: No metastases
- CT-guided biopsy: Adenocarcinoma, TTF-1 positive
- **Molecular testing**:
  - EGFR mutation: Exon 19 deletion (sensitizing mutation)
  - ALK: Negative
  - ROS1: Negative
  - PD-L1: 60%

### Diagnosis
Stage IIB (T3N1M0) Non-Small Cell Lung Cancer - Adenocarcinoma with EGFR Exon 19 Deletion

### Treatment
1. **Multidisciplinary tumor board review**
2. **Surgical resection**: Right lower lobectomy with mediastinal lymph node dissection
3. **Adjuvant therapy**: Given positive EGFR mutation:
   - Adjuvant osimertinib (EGFR TKI) for 3 years (ADAURA trial)
   - Significant reduction in recurrence risk
4. Surveillance: CT chest every 6 months for 2 years, then annually
5. Genetic counseling if any family history of cancer

### Physiological Principles Demonstrated
- **EGFR mutation epidemiology**: EGFR mutations are more common in adenocarcinomas, never-smokers, women, and Asian patients. Up to 50% of Asian never-smokers with adenocarcinoma harbor EGFR mutations.
- **Driver mutation concept**: Lung cancer with driver mutations (EGFR, ALK, ROS1) is "oncogene addicted" - tumor survival depends on the mutated pathway, making it exquisitely sensitive to targeted inhibitors.
- **Sensitizing vs. resistance mutations**: Exon 19 deletions and exon 21 L858R are sensitizing mutations. T790M is a resistance mutation that develops on first/second-generation TKIs (osimertinib covers this).
- **Personalized medicine**: Comprehensive molecular testing is standard of care to identify targetable mutations and guide therapy selection.

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## Case 2: Small Cell Lung Cancer - Paraneoplastic Syndrome

### Clinical Image
![Small Cell Lung Cancer](case_01_image.jpg)
*Source: [Wikimedia Commons - Small cell lung cancer](https://commons.wikimedia.org/wiki/File:Small_cell_lung_cancer_-_cytology.jpg) - 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
1. Extensive Stage Small Cell Lung Cancer
2. Lambert-Eaton Myasthenic Syndrome (paraneoplastic)
3. SIADH (paraneoplastic hyponatremia)

### Treatment
1. **Chemotherapy + Immunotherapy**:
   - Platinum (carboplatin) + etoposide + durvalumab or atezolizumab
   - First-line standard for extensive stage SCLC
2. Fluid restriction for SIADH
3. **Treatment of underlying cancer often improves LEMS**
4. Symptomatic LEMS treatment: 3,4-diaminopyridine (amifampridine)
5. Prophylactic cranial irradiation (PCI) if good response to treatment
6. Surveillance for brain metastases
7. 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%.

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## Case 3: Pancoast Tumor - Superior Sulcus Syndrome

### Clinical Image
![Pancoast Tumor MRI](case_01_image.jpg)
*Source: [Wikimedia Commons - Pancoast tumor](https://commons.wikimedia.org/wiki/File:Pancoast_tumor.jpg) - CC BY-SA 3.0*

### Patient Presentation
A 55-year-old man presents with 3 months of progressively worsening right shoulder and arm pain radiating down the inner aspect of his arm to his fourth and fifth fingers. He has seen an orthopedist and physical therapist without improvement. He also noticed his right eyelid drooping and he sweats less on the right side of his face. He has smoked 2 packs per day for 35 years.

### Demographics
- Age: 55 years
- Sex: Male
- Past Medical History: None significant
- Medications: NSAIDs for pain (ineffective)
- Social History: 70 pack-year smoking history, current smoker

### Chief Complaint
Right shoulder and arm pain, eyelid drooping, and facial changes

### Physical Examination
- Blood pressure: 136/84 mmHg
- Heart rate: 82 bpm
- General: Appears uncomfortable due to pain
- HEENT: Right-sided ptosis, miosis, anhidrosis on right side of face (Horner syndrome)
- Neck: No adenopathy
- Respiratory: Decreased breath sounds at right apex
- Neurological:
  - Weakness and atrophy of right intrinsic hand muscles (C8-T1)
  - Decreased sensation along ulnar distribution (C8-T1)
  - Triceps reflex diminished on right

### Workup
- Chest X-ray: Asymmetric apical opacity on right (initially interpreted as pleural thickening)
- CT chest: 4.5 cm right apical mass extending into the thoracic inlet, adjacent rib destruction (first and second ribs), invasion of right brachial plexus
- MRI chest/brachial plexus: Confirms invasion of lower brachial plexus (C8-T1 roots), involvement of subclavian vessels, no vertebral body invasion
- PET-CT: FDG-avid apical mass, ipsilateral hilar node, no distant metastases
- CT-guided biopsy: Squamous cell carcinoma
- Brain MRI: No metastases

### Diagnosis
Stage IIIA Pancoast Tumor (Superior Sulcus Tumor) - Squamous Cell Carcinoma with:
- Brachial plexus invasion (C8-T1)
- Horner syndrome (stellate ganglion involvement)
- Chest wall invasion

### Treatment
1. **Induction chemoradiation**:
   - Concurrent cisplatin-based chemotherapy with radiation
   - 45-50 Gy over 5 weeks
2. **Restaging** after induction
3. **Surgical resection** (if responding):
   - En bloc resection including chest wall, involved ribs, lower brachial plexus roots
   - Goal: R0 resection (negative margins)
4. Pain management (neuropathic pain regimen: gabapentin, opioids)
5. Smoking cessation (though damage done, still beneficial)
6. Long-term surveillance

### Physiological Principles Demonstrated
- **Pancoast syndrome anatomy**: Tumors at the lung apex (superior sulcus) invade adjacent structures: brachial plexus (C8-T1 causing arm pain and weakness), stellate ganglion (Horner syndrome), subclavian vessels, ribs, and vertebrae.
- **Horner syndrome triad**: Ptosis (sympathetic innervation to Muller muscle), miosis (pupil dilator), anhidrosis (facial sweating) - caused by interruption of the sympathetic chain at the stellate ganglion.
- **Pain pattern**: Lower brachial plexus involvement causes pain and weakness in the ulnar distribution (C8-T1), often misdiagnosed as musculoskeletal or cervical spine disease.
- **Multimodality treatment necessity**: Pancoast tumors require combined modality therapy (chemoradiation followed by surgery) for best outcomes; surgery alone has high local recurrence rates.