What is lung cancer adenocarcinoma?

Lung Cancer Adenocarcinoma: Classification, Diagnosis, and Management

Lung adenocarcinoma is a distinct subtype of non-small cell lung cancer with specific histological, molecular, and clinical characteristics that requires precise classification for optimal treatment selection and prognostication. 1

Classification and Histopathology

Adenocarcinoma is the most common histologic type of lung cancer, characterized by glandular differentiation, papillary structures, and cytoplasmic mucin vacuoles. The current classification system has evolved significantly, with important changes including:

• Elimination of bronchioloalveolar carcinoma (BAC) terminology - this outdated term is strongly discouraged 1
• New classification categories:
  • Adenocarcinoma in situ (AIS) - formerly BAC: <3 cm nodule with pure lepidic growth, no invasion 1
  • Minimally invasive adenocarcinoma (MIA) - <3 cm nodule with ≤5 mm invasion 1
  • Invasive adenocarcinoma - with predominant growth patterns:
    • Lepidic (>5 mm invasion)
    • Acinar
    • Papillary
    • Micropapillary
    • Solid with mucin 1
  • Invasive adenocarcinoma variants:
    • Mucinous adenocarcinoma
    • Colloid
    • Fetal
    • Enteric 1, 2

Diagnostic Approach

Accurate diagnosis requires:

1. Histopathological examination - The gold standard for diagnosis

2. Immunohistochemistry (IHC) - Essential for differentiating adenocarcinoma from other lung cancers:

   • TTF-1 (thyroid transcription factor-1) - Positive in 70-100% of non-mucinous adenocarcinomas 1
   • Napsin A - Expressed in >80% of lung adenocarcinomas 1
   • CK7+/CK20- pattern - Typical for primary lung adenocarcinoma 1

3. Molecular testing - Critical for treatment selection:

   • EGFR mutation - Present in 10% of Western and up to 50% of Asian patients 1
   • KRAS mutation - Associated with resistance to tyrosine kinase inhibitors 1
   • ALK gene rearrangement - Important for targeted therapy selection 1, 2

Clinical Significance and Prognosis

• Early-stage disease (AIS and MIA):

  • Complete resection of AIS offers 100% disease-specific survival 1, 2
  • MIA has near 100% disease-specific survival after complete resection 2

• Advanced disease:

  • Adenocarcinoma diagnosed by morphology has better prognosis than "NSCLC favor adenocarcinoma" (diagnosed by IHC only) 3
  • 5-year survival rates range from 52% for localized disease to 3.7% for metastatic disease 4

Management Considerations

1. Molecular profiling is essential:

   • All patients with adenocarcinoma should be tested for EGFR mutations 1, 2
   • Testing for ALK gene rearrangements is recommended 1
   • EGFR mutations predict responsiveness to EGFR tyrosine kinase inhibitors 2
   • EGFR and KRAS mutations are mutually exclusive 1

2. Tissue management:

   • Judicious use of IHC studies on small tissue samples is recommended to preserve tissue for molecular testing 1
   • Fresh cryopreserved tumor tissue should be considered for advanced molecular studies 1

3. Staging considerations:

   • T factor should be adjusted according to only the invasive component in tumors with lepidic areas 2
   • Radiologically, measurement of the solid component of part-solid nodules is important 2, 5

Pitfalls and Caveats

• Avoid using generic "NSCLC" terminology - More specific classification is critical for treatment selection 1, 2
• Beware of misdiagnosis - Mesothelioma can mimic adenocarcinoma; use appropriate IHC panels for differentiation 1
• Consider tumor heterogeneity - Lung adenocarcinomas may exhibit clonal heterogeneity with different combinations of mutations 6
• Monitor for clonal evolution - Molecular profiles can change during treatment, requiring reassessment 6
• Early detection is critical - CT screening can identify ground glass nodules representing early adenocarcinoma spectrum lesions 5

Adenocarcinoma spectrum lesions represent a continuum from pre-invasive to invasive disease, with opportunities for early intervention that may significantly improve survival outcomes 5.