PANCE Blueprint Pulmonary (10%)

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.

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 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: CAN NOT be treated with surgery 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)

< 3 cm is a nodule (coin lesion) > 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 pulmonary nodule recommendations

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