Lung Tumors

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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. Small Cell Lung Cancer in Lung

⭐ 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.

Squamous cell carcinoma histology features

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.

Electron micrograph of small cell lung cancer

⭐ 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).

Practice Questions: Lung Tumors

Test your understanding with these related questions

What is the T stage of a 2.5cm lung carcinoma, not involving the pleura?

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Flashcards: Lung Tumors

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Histopathology showing the _____ effect are suggestive of a small cell carcinoma of the lung.

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Histopathology showing the _____ effect are suggestive of a small cell carcinoma of the lung.

Azzopardi

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