PANCE Blueprint Pulmonary (9%)

ReelDx Virtual Rounds (lung cancer)

1. Non–Small Cell Lung Cancer (NSCLC) - About 85% of cases

Subtypes include: adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and carcinoid tumors (rare neuroendocrine tumors, not always included under NSCLC).

1. Adenocarcinoma
   • Most common subtype of NSCLC (35-40% of cases)
   • Common in non-smokers but also associated with smoking and asbestos exposure
   • Paraneoplastic syndrome: thrombophlebitis
   • Presentation → non-smoker, with an incidental finding of a small peripheral lesion
2. Squamous Cell Carcinoma
   • 25-35% of cases
   • Typically central, arising from bronchial tissue, associated with smoking
   • Often causes hemoptysis due to tumor invading the central bronchus
   • Paraneoplastic syndrome: hypercalcemia (via PTHrP production)
   • Presentation → smoker with hemoptysis and a large central mass on imaging
3. Large Cell Carcinoma
   • Rare (5% of cases)
   • Poorly differentiated, high-grade tumors
   • Typically peripheral (60%)
   • Paraneoplastic syndrome: gynecomastia
   • Presentation → smoker with a large peripheral mass, often asymptomatic until late-stage
4. Carcinoid Tumors (Rare, 1-2% of all lung cancers)
   • Derived from neuroendocrine cells and can secrete serotonin, histamine, and bradykinin
   • Primary lung carcinoid tumors are rare, but metastases from GI carcinoids (e.g., appendix → liver → lung) are possible
   • Presentation → hemoptysis, cough, focal wheezing, recurrent pneumonia; may cause carcinoid syndrome (flushing, diarrhea, wheezing, hypotension)
   • Note: Most carcinoid tumors are slow-growing and less aggressive compared to other lung cancers

2. Small Cell Lung Cancer (SCLC) - About 15% of cases

• Extremely aggressive, almost exclusively seen in smokers
• Rapid progression, with 80% of cases metastatic at diagnosis
• Poor prognosis, not amenable to surgery, treated with chemotherapy and radiation
• Paraneoplastic syndromes:
  • ACTH secretion → Cushing syndrome
  • ADH secretion → hyponatremia (SIADH)
  • Lambert-Eaton Myasthenic Syndrome: Autoantibodies affecting calcium channels → proximal muscle weakness

DX: Chest X-ray followed by CT scan, confirmed with biopsy (bronchoscopy, CT-guided needle biopsy, or thoracoscopy)

• Staging: TNM system (Tumor, Node, Metastasis)

TX:

Non-small cell cancer can be treated with surgery

• Treatment depends on staging:
  • Stage 1-2 surgery
  • Stage 3 Chemo, then surgery
  • Stage 4 palliative
  • Carcinoid tumors are treated with surgery

Small cell cancer CANNOT be treated with surgery, and will need chemotherapy

Associated manifestations:

• Superior vena cava syndrome (facial/arm edema and swollen chest wall veins)
• Pancoast tumor (shoulder pain, Horner’s syndrome, brachial plexus compression)
• Horner’s syndrome (unilateral miosis, ptosis, and anhidrosis)
• Carcinoid syndrome (flushing, diarrhea, and telangiectasia)

Small cell cancer of the lung with a typical centrally located mediastinal mass (seen here on the left)

A tumor arising from neuroendocrine cells → leading to excess secretion of serotonin, histamine, and bradykinin

• Common primary sites include GI (small and large intestines, stomach, pancreas, liver), lungs, ovaries, and thymus
  • The most common site of a neuroendocrine (carcinoid) tumor to metastasize to is the liver
  • Carcinoid tumor of the appendix is the most common cause. The appendiceal cancer travels from the appendix then to the liver where it metastasizes to the lungs
• Usually asymptomatic until liver metastasis; symptoms develop occasionally
  • GI tract tumor→ hormone secretion → enter into enterohepatic circulation → liver inactivates hormones → no symptoms
  • Liver tumor → hormone secretion → released into circulation + liver dysfunction → symptoms
• Carcinoid syndrome (the hallmark sign) = Cutaneous flushing, diarrhea, wheezing and low blood pressure is actually quite rare and occurs in ~ 5% of carcinoid tumors and becomes manifest when vasoactive substances from the tumors enter the systemic circulation escaping hepatic degradation.
• The syndrome includes flushing, ↑ intestinal motility (diarrhea), itching and less frequently, heart failure, vomiting, bronchoconstriction, asthma, and wheezing
  • ↑ Serotonin leads to collagen fiber thickening, fibrosis = heart valve dysfunction → tricuspid regurgitation, pulmonary stenosis/bronchoconstriction, and wheezing
  • ↑ Histamine and bradykinin = vasodilation and flushing
  • ↑ serotonin synthesis → ↓ tryptophan → ↓ niacin/B3 synthesis = pellagra

DX:

CT-Scan to locate the tumors

• • Octreoscan → radiolabeled somatostatin analog (octreotide) binds to somatostatin receptors on tumor cells
  • Urinalysis → elevated 5-hydroxyindoleacetic acid (5-HIAA) → is the main metabolite of serotonin and is used to determine serotonin levels in the body
  • Pellagra (niacin/B3 deficiency) - ↑ serotonin synthesis → ↓ tryptophan → ↓ niacin/B3 synthesis
  • Chest X-ray shows low-grade CA seen as pedunculated sessile growth in the central bronchi
  • Bronchoscopy- pink/purple central lesion, well-vascularized

Treatment is by surgical excision and carries a good prognosis

• The lesions are resistant to radiation therapy and chemotherapy
• Octreotide - a somatostatin analog that binds the somatostatin receptors and decreases the secretion of serotonin by the tumor
• Niacin supplementation

Carcinoid tumors are usually centrally located, arising in large airways. The arrow points to the tumor in the right hilar region.

< 3 cm is a nodule (coin lesion), and > 3 cm, the lesion is considered a "mass"

• Smooth, well-defined edges are more likely to be benign
• Ill-defined, lobular, or spiculated suggests cancer
• Pulmonary nodules are also known as coin lesions

When managing pulmonary nodules, we follow the Fleischner Society's pulmonary nodule recommendations

Chest X-ray showing a solitary pulmonary nodule (indicated by a black box) in the left upper lobe