Adenocarcinoma of the lung pathophysiology

Adenocarcinoma of the Lung Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Adenocarcinoma of the Lung from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Study of Choice
Staging
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
X Ray
Echocardiography and Ultrasound
CT
MRI
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Intervention
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Adenocarcinoma of the lung pathophysiology On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Adenocarcinoma of the lung pathophysiology All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Adenocarcinoma of the lung pathophysiology
CDC on Adenocarcinoma of the lung pathophysiology
Adenocarcinoma of the lung pathophysiology in the news
Blogs on Adenocarcinoma of the lung pathophysiology
Directions to Hospitals Treating Adenocarcinoma of the lung
Risk calculators and risk factors for Adenocarcinoma of the lung pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shanshan Cen, M.D. [2] Sudarshana Datta, MD [3]

Overview

Adenocarcinoma is the most common type of lung cancer found in non-smokers and is usually seen as a peripheral lesion in the lungs. Individual susceptibility, active smoking, radon exposure, exposure to high pollution levels, asbestos exposure, occupational or environmental exposure to particular agents or carcinogens contribute to the development of adenocarcinoma of the lung. Hydrocarbons cause damage to the DNA and form DNA adducts. Benzo-A-pyrine has effects on inducing p53 mutations and affects molecular signaling pathways such as AKT. Genes involved in the pathogenesis of adenocarcinoma of the lung include EGFR, HER2, KRAS, ALK, and BRAF. On gross pathology, peripheral multifocal lesions are characteristic findings in patients with adenocarcinoma of the lung. On microscopic histopathological analysis, nuclear atypia, eccentrically placed nuclei, abundant cytoplasm, and conspicuous nucleoli are characteristic findings of adenocarcinoma of the lung.

Pathogenesis

• Adenocarcinoma is the most common type of lung cancer found in non-smokers and is usually seen as a peripheral lesion in the lungs, as compared to centrally located tumors such as small cell lung cancer and squamous cell lung cancer.

• Individual susceptibility, active smoking, radon exposure, exposure to high pollution levels, asbestos exposure, occupational or environmental exposure to particular agents or carcinogens contribute to the development of adenocarcinoma of the lung. Hydrocarbons cause damage to the DNA and form DNA adducts. Benzo-A-pyrine has effects on inducing p53 mutations and affects molecular signaling pathways such as AKT.
• The “multiple hit theory” for adenocarcinoma of the lung states that genetic reproduction is hindered due to the cumulative effect of several toxic insults. Underlying lung disease such as COPD, idiopathic pulmonary fibrosis and tuberculosis may exacerbate also trigger the process.
• Mutations involving several oncogenes may lead to the development of adenocarcinoma of the lung. These are as follows:
  • Mutations of ras (found in thirty percent of cases) affect signal transduction by affecting GTPase activity:
    • H-ras
    • K-ras, also determines patient prognosis
    • N-ras
  • c-myc
  • c-raf
  • Tumor suppressor genes retinoblastoma (Rb) and p53
  • Mutations of APOBEC protein

Genetics

• Genes involved in the pathogenesis of adenocarcinoma of the lung include:
  • EGFR (7p11)
  • KRAS (12p12)
  • BRAF (7q34)
  • PIK3CA (3q26)
  • ERBB2 (17q12)
  • Translocation EML4/ALK
  • Tyrosine kinase fusions
  • ALK (2p23), ROS1 (6q22), and RET (10q11)

Gross Pathology

• On gross pathology, peripheral multifocal lesions are characteristic findings in patients with adenocarcinoma of the lung.

Gray-tan tumor seen predominantly at the periphery.
Source: Libre pathology

Microscopic Pathology

Micrograph of mucinous adenocarcinoma of the lung, H&E stain.
Source: Libre pathology

Micrograph showing an adenocarcinoma of the lung (acinar pattern), H&E stain.
Source: Libre pathology

• On microscopic histopathological analysis, nuclear atypia, eccentrically placed nuclei, abundant cytoplasm, and conspicuous nucleoli are characteristic findings of adenocarcinoma of the lung.
• Atypical adenomatous hyperplasia (AAH): is the precursor of peripheral adenocarcinomas. It consists of well demarcated columnar or cuboidal cells with the following features:
  • Varying degrees of cytologic atypia
  • Hyperchromasia
  • Pleomorphism
  • Prominent nucleoli
• As adenocarcinoma is a derivative of mucus producing glands in the lungs, it tends to stain mucin positive.
• Based on differentiation, the tumor may be:
  • Well differentiated (low grade) : Normal appearance
  • Poorly differentiated (high grade): Abnormal glandular appearance with a positive mucin stain

Histological Subtypes

• Histologically adenocarcinoma is divided in to following subtypes:
• The IASLC/ATS/ERS lung adenocarcinoma histologic classification system was proposed in the Journal of Thoracic Oncology in 2011.
• According to this new classification, tumor size ≤3 cm with pure lepidic pattern, but without lymphatic, vascular, pleural invasion or tumor necrosis was defined as adenocarcinoma in situ (AIS).
• If tumor size ≤3 cm with a lepidic predominant pattern and contained ≤5 mm stromal invasion it was defined as minimally invasive adenocarcinoma (MIA).
• If tumor had >5 mm stromal invasion it was defined as an invasive adenocarcinoma.
  • Lepidic adenocarcinoma
    • Lepidic growth adenocarcinoma is defined as tumor cells proliferating along the surface of intact alveolar walls without stromal or vascular invasion pathologically.
    • Solitary adenocarcinomas with pure lepidic growth, termed “AIS” has 100% disease-specific survival, if the lesion is completely resected.
  • Acinar adenocarcinoma:
    • Acinar pattern comprises infiltrating round to oval glands lined by tumour cells.
    • Irregular-shaped glands.
    • Malignant cells: Hyperchromatic nuclei, fibroblastic stroma.
    • Sometimes the glandular cells and lumina may contain mucin.
  • Papillary adenocarcinoma
    • The papillary pattern is composed of glandular tumour cells growing along fibrovascular cores.
    • Papillae, necrosis, surrounding invasion, cuboidal to columnar epithelial lining, mucinous or non-mucinous.
    • Lung adenocarcinomas with papillary growth show 2 types of papillary architecture:
      • True papillary type: Papillae containing a layered glandular epithelium surrounded by fibrovascular core.
      • Micropapillary type: The papillary tufts lack a central fibrovascular core and extensively shed within alveolar spaces.
  • Micropapillary adenocarcinoma:
    • The papillary tufts lack a central fibrovascular core and extensively shed within alveolar spaces.
    • Micropapillary growth has been associated with an aggressive clinical course compared with traditional papillary adenocarcinoma.
    • Micropapillary adenocarcinoma (MPA) may be often diagnosed at a high stage in nonsmokers, with intralobar satellites.
    • Micropapillary adenocarcinoma frequently metastasizes to the contralateral lung, mediastinal lymph nodes, bone, and adrenal glands, with high mortality.
  • Solid adenocarcinoma
  • Invasive mucinous adenocarcinoma
    • Mixed invasive mucinous
    • Nonmucinous adenocarcinoma
  • Colloid adenocarcinoma
  • Fetal adenocarcinoma
  • Enteric adenocarcinoma
  • Minimally invasive adenocarcinoma
    • Nonmucinous
    • Mucinous:
      • Low grade differentiation
      • Composed of: Tall columnar cells, basal nuclei and pale cytoplasm resembling goblet cells
      • Varying amounts of cytoplasmic mucin and cytologic atypia
  • Preinvasive lesions
    • Atypical adenomatous hyperplasia
    • Adenocarcinoma in situ
      • Nonmucinous
      • Mucinous

References

Template:WikiDoc Sources