Lung Tumors

Lung Tumors: Overview - Classifying Cough Culprits

• Primary Classification:
  • Small Cell Lung Cancer (SCLC): ~15%; neuroendocrine, aggressive, rapid growth, early metastases. Often central.
  • Non-Small Cell Lung Cancer (NSCLC): ~85%; includes:
    • Adenocarcinoma: Most common (~40%), esp. non-smokers, women. Peripheral. Glandular.
    • Squamous Cell Carcinoma (SCC): ~25-30%; strong smoking link. Central, cavitating. Keratin pearls.
    • Large Cell Carcinoma: ~10%; undifferentiated, diagnosis of exclusion. Poor prognosis.
• Epidemiology: Leading cause of cancer death. Peak incidence 55-65 years.
• Major Risk Factors:
  • Tobacco smoke: ~85% (active/passive).
  • Occupational: Asbestos, radon, arsenic.
  • Air pollution; Genetic predisposition.

⭐ Adenocarcinoma is the most common lung cancer subtype in never-smokers and women.

Lung Tumors: Squamous & Adenocarcinoma - The NSCLC Giants

• Non-Small Cell Lung Cancer (NSCLC): Comprises ~85% of lung cancers; SCC & Adeno are major subtypes.
• Squamous Cell Carcinoma (SCC)
  • Location: Central. 📌 SCC C's: Central, Cigarettes, hyperCalcemia, Cavitation.
  • Risk: Strongest link to Smoking.
  • Histo: Keratin pearls, intercellular bridges; p40+.
  • Clinical: Obstruction; Paraneoplastic: Hypercalcemia (PTHrP).
  • Gross: Often cavitates.
• Adenocarcinoma
  • Location: Peripheral.
  • Risk: Most common in non-smokers, women, overall.
  • Histo: Glands, mucin; TTF-1+, Napsin A+.
  • Subtypes: Acinar, papillary, lepidic (formerly BAC).
  • Molecular: EGFR, ALK, ROS1, KRAS mutations (targetable).

  ⭐ Adenocarcinoma in situ (AIS), pure lepidic pattern, excellent prognosis if resected.

Lung Tumors: SCLC & Other Types - Small Cells, Big Trouble

• Small Cell Lung Cancer (SCLC)
  • Highly aggressive neuroendocrine tumor (~15% lung cancers); strong smoking link.
  • Central; rapid growth, early metastasis.
  • Micro: Small, dark blue cells (Kulchitsky); scant cytoplasm, nuclear molding, Azzopardi phenomenon.
  • Markers: Chromogranin A, Synaptophysin, CD56.
  • Paraneoplastic: SIADH, Cushing's (ACTH), LEMS (anti-presynaptic $Ca^{2+}$ channels Abs).
  • 📌 Smokers, Sentral, Syndromes, Sensitive (chemo/radio), Swift.
• Large Cell Carcinoma
  • Undifferentiated NSCLC; diagnosis of exclusion. Peripheral/central.
  • Large cells, prominent nucleoli; poor prognosis.
• Carcinoid Tumors
  • Low-grade neuroendocrine malignancy (<5% lung tumors).
  • Types:
    • Typical: Central, polypoid; uniform cells; good prognosis.
    • Atypical: Peripheral/central; ↑mitoses, necrosis; higher metastatic risk.

⭐ Lambert-Eaton Myasthenic Syndrome (LEMS), targeting presynaptic calcium channels, is a characteristic paraneoplastic syndrome of SCLC.

Lung Tumors: Molecular Path & Staging - Genes, Spread, Grim Outlook

• Molecular Pathogenesis: NSCLC (esp. AdenoCA) driver mutations guide targeted therapy.
  • EGFR: Mutated in ~15% (non-smokers). Therapy: Osimertinib.
  • ALK rearrangement: ~5%. Therapy: Alectinib.
  • ROS1 rearrangement: ~1-2%. Therapy: Crizotinib.
  • KRAS: ~25% (smokers). G12C specific: Sotorasib.
  • PD-L1 expression: Immunotherapy biomarker (e.g. Pembrolizumab); ↑ predicts response.
• Staging: TNM (8th ed.) critical. Defines anatomical extent (T,N,M), guides prognosis & therapy.
• Spread:
  • Lymphatic (nodes) & hematogenous.
  • Common sites: Brain, Bone, Adrenals, Liver (📌 BLAB).
• Grim Outlook:
  • Overall 5-year survival ~20%.
  • SCLC: Highly aggressive, early metastasis, poor prognosis.
  • NSCLC: Stage IV challenging; targeted/immuno therapies improve survival.

⭐ KRAS mutations (smokers, adenoCA) once "undruggable", now G12C targeted (Sotorasib).

High‑Yield Points - ⚡ Biggest Takeaways

• Adenocarcinoma: Most common lung cancer, especially in non-smokers; often peripheral; TTF-1 positive.
• Squamous Cell Carcinoma: Strong smoking link; central; hypercalcemia (PTHrP); keratin pearls.
• Small Cell Carcinoma: Aggressive; smoking-related; central; paraneoplastic syndromes (SIADH, LEMS); neuroendocrine markers.
• Pancoast Tumor: Apical tumor causing Horner's syndrome, shoulder pain, and arm weakness.
• Key mutations: EGFR (non-smoker AdenoCa), KRAS (smoker AdenoCa), ALK (younger AdenoCa).