Pulmonary Carcinoma Notes

Pulmonary Carcinoma

Definition

  • Pulmonary carcinoma is a common neoplastic pathology.
  • It is characterized by aggressive growth of transformed cells in the lungs.
  • It has the potential to invade surrounding tissue and spread to other organs (brain, bones, liver).
  • 90-95% of lung cancers arise from epithelial cells of the bronchus and bronchioles.
  • It can also develop from the pleura (mesothelioma) and, in rare cases, from the supporting tissue.
  • Lung cancer is more common in men than in women.

Etiology

  • The major cause is smoking and tobacco use.
  • Cigarette smoke contains more than 4,000 chemicals, of which 40 are known to be carcinogenic, and 20 can cause lung cancer.
  • The risk is increased for smokers who started before the age of 25 and for those who have smoked one or more packs a day for 20 years.
  • Exposure to asbestos increases the risk five times.
  • Other causes include:
    • Passive smoking
    • Radon gas
    • Metals (nickel, chrome)
    • Organic chemicals (benzene)
    • Occupational radiation
    • Polluted air

Genetic and Molecular Basis

  • Lung cancer, like other cancers, is caused by a genetic mutation influenced by predisposing factors.
  • At the molecular level, it is characterized by:
    • The presence of oncogenes (genes that promote uncontrolled cell division).
    • The inactivation of suppressor genes.
  • Tumor development is supported by epidermal growth factor.

Oncogenes and Suppressor Genes

  • The myc family of oncogenes plays an important role in the main pathophysiological mechanism, being the most common molecular abnormality identified in small cell lung carcinoma (SCLC).
  • Other oncogenes that amplify the pathogenesis of SCLC may include c-raf, c-erb-b1, and c-fms.
  • The retinoblastoma suppressor gene (Rb), located at chromosome 13, is missing in 60% of SCLC cases.
  • In large cell lung carcinoma (LCLC), the ras oncogenes family is involved (H-ras, K-ras, N-ras).

Classification of Lung Cancer

  • Lung Cancer (LC)
    • Non-small cell Lung Cancer (NSCLC) (~85%)
      • Adenocarcinoma (LUAD)
        • Origin: Alveolar type II Epithelial Cell
      • Squamous-cell Carcinoma (LUSC)
        • Origin: Epithelial Cell
      • Large-cell Carcinoma (LCC)
        • Origin: Various Epithelial Cells
    • Small-cell Lung Cancer (SCLC) (~15%)
      • Origin: Neuroendocrine cell; Basal

Paraneoplastic Syndromes

  • One of the known pathophysiological features of lung cancer is the paraneoplastic syndrome.
  • Paraneoplastic syndrome consists of a complex of symptoms that are not expected with the onset of cancer and cannot be explained by obvious characteristics of the tumor.
  • It is an alarm signal that warns of possible tumor damage, sometimes having a role in the early detection of the tumor.
  • It is characterized by excessive production of hormones and cytokines.

Specific Paraneoplastic Syndromes

  • Small cell lung carcinoma (SCLC)
    • ADH production: Water retention, hyponatremia
    • ACTH production: Cushing's disease (muscle atrophy, hypercorticism, full moon face, hyperglycemia, hypertension, hyperpigmentation)
    • Production of foreign proteins at the neuromuscular junction: Eaton-Lambert syndrome (muscle weakness in the lower limbs)
  • Squamous cell carcinoma (SCC)
    • Parathyroid hormone-related proteins: Hypercalcemia
  • Adenocarcinoma
    • Procoagulation factors: Trousseau syndrome (clot formation in the lower venous system)

Signs and Symptoms

  • Progressive fatigue and generalized weakness
  • Loss of appetite
  • Weight loss
  • Aggravation of cough
  • Difficulty swallowing
  • Difficulty breathing
  • Wheezing
  • Hemoptysis
  • Significant pain in the case of dissemination in the skull, hip, etc., in the brain with the appearance of visual problems, vomiting, altered mental status.

Positive Diagnosis

  • Based on:
    • Chest X-ray PA and LL
    • Bronchoscopy
    • Cytological examination of sputum
    • Fine needle parenchyma biopsy
    • Lymph node biopsy
    • Chest and abdominal CT
    • MRI, especially if suspected
    • Pulmonary ultrasonography
  • Definitive diagnosis requires confirmation of sputum tumor cells, bronchial lavage, biopsy.

Treatment

  • Depends on the type, stage, and biological condition of the patient:
    • Surgical
    • Radiotherapy
    • Chemotherapy

Complications and Prognosis

  • Intense pain due to bone metastases
  • Vision disorders, vomiting, abolition of the mental status due to brain metastases.
  • Pneumonia, repeated pleurisy (paraneoplastic pneumonia, metastatic pleurisy-M1a)
  • Hemoptysis, anemia
  • In the case of ADH-secreting tumors, hyponatremia occurs.
  • In the case of ACTH-secreting tumors, elevated and oscillating blood pressure values.
  • Side effects of treatments
  • Mortality at one year reaches 42%, and at five years, only 15% of patients survive.
  • Small cell carcinoma is one of the most aggressive cancers, with an average survival of only 2-4 months after diagnosis.