Lung tumors (primary and metastatic)

Lung Tumor Basics - A Malignant Divide

• Primary vs. Metastatic: Lungs are a frequent target for metastases (mets), often more common than primary tumors. Mets are typically multiple and peripheral.
• Primary tumors are divided based on histology, which dictates treatment.

⭐ The SCLC vs. NSCLC distinction is paramount. SCLC is typically treated with chemotherapy/radiation due to early metastasis, whereas NSCLC may be amenable to surgical resection.

Small Cell Lung Cancer - Tiny Cells, Big Syndromes

• Central location, aggressive, strong link to smoking.
• Neuroendocrine origin: Kulchitsky cells (APUD cells).
• Histology: Small, dark blue cells; scant cytoplasm, nuclear molding.
• Paraneoplastic Syndromes are common:
  • SIADH (hyponatremia)
  • Cushing Syndrome (ectopic ACTH)
  • Lambert-Eaton Myasthenic Syndrome

⭐ Lambert-Eaton Syndrome: Antibodies against presynaptic Ca²⁺ channels cause proximal muscle weakness that improves with use.

NSCLC: Adenocarcinoma - The Peripheral Player

• Most common primary lung cancer overall, especially in non-smokers, women, and patients < 45 years old.
• Location: Typically peripheral, arising from alveolar glandular epithelium (Type II pneumocytes, Clara cells).
• Histology: Shows glandular differentiation (acini) and/or mucin production. Key precursor: Atypical Adenomatous Hyperplasia (AAH).
• Genetics: EGFR mutations (in non-smokers), KRAS (in smokers), and ALK rearrangements are common drivers, guiding targeted therapy.

⭐ Lepidic growth pattern (formerly Bronchioloalveolar Carcinoma/BAC) involves spread along alveolar septa without invasion, often appearing as a hazy ground-glass opacity on CT.

NSCLC: Squamous & Large Cell - The Central Smokers

• Squamous Cell Carcinoma (SCC)

  • Location: Central, arising from major bronchi.
  • Risk Factors: Overwhelmingly associated with smoking.
  • Pathognomonic Features: Keratin pearls and intercellular bridges on histology.
  • Paraneoplastic Syndrome: Ectopic PTHrP secretion → Hypercalcemia.
  • 📌 Mnemonic: The 4 Cs: Central, Cigarettes, hyperCalcemia, Cavitation.

• Large Cell Carcinoma

  • Location: Typically peripheral, but can be central.
  • Diagnosis: Undifferentiated tumor, diagnosis of exclusion. Poor prognosis.
  • Histology: Sheets of large pleomorphic cells, prominent nucleoli.

⭐ Hypercalcemia from PTHrP is a classic board presentation for Squamous Cell Carcinoma.

Other Tumors & Mets - Cannonball Catastrophe

• Bronchial Carcinoid: Low-grade neuroendocrine malignancy. Can cause carcinoid syndrome (flushing, diarrhea), but rare. Histology: nests of uniform cells, "salt-and-pepper" chromatin.
• Hamartoma: Most common benign lung tumor; disorganized cartilage, fibrous tissue, and fat. Imaging shows "popcorn" calcification.
• Metastases: More common than primary lung cancer. Typically multiple, spherical, bilateral nodules.

⭐ Common primary sites for "cannonball" metastases include renal cell carcinoma and choriocarcinoma.

• Smoking is the leading cause of lung cancer; adenocarcinoma is the most common type in non-smokers.
• Metastases from other sites (e.g., breast, colon) are more common in the lungs than primary tumors.
• Remember central (Squamous, Small Cell) vs. peripheral (Adenocarcinoma, Large Cell) locations.
• Small Cell Lung Cancer (SCLC) is aggressive and notorious for paraneoplastic syndromes (SIADH, Cushing).
• Squamous Cell Carcinoma (SCC) is linked to hypercalcemia (PTHrP).
• A Pancoast tumor in the superior sulcus can cause Horner syndrome.