Adenocarcinoma of the lung pathophysiology

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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

Subtypes

• Lepidic predominant:

• Tumor grows long the alveolar wall

• Acinar predominant:

• Berry-shaped glands, smaller than lung acini

• Papillary predominant:

• Fibrovascular cores

• Micropapillary predominant:

• Nipple shaped projections without fibrovascular cores

• Solid predominant:

• Sheet of cells

References

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