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Non-Small Cell Lung Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Cellular Classification of NSCLC

Malignant non-small cell epithelial tumors of the lung are classified by the World Health Organization (WHO)/International Association for the Study of Lung Cancer (IASLC). There are three main subtypes of non-small cell lung cancer (NSCLC), including the following:

  • Squamous cell carcinoma (25% of lung cancers).
  • Adenocarcinoma (40% of lung cancers).
  • Large cell carcinoma (10% of lung cancers).

There are numerous additional subtypes of decreasing frequency.[1]

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WHO/IASLC Histologic Classification of NSCLC

  1. Squamous cell carcinoma.
    1. Papillary.
    2. Clear cell.
    3. Small cell.
    4. Basaloid.
  2. Adenocarcinoma.
    1. Acinar.
    2. Papillary.
    3. Bronchioloalveolar carcinoma.
      1. Nonmucinous.
      2. Mucinous.
      3. Mixed mucinous and nonmucinous or indeterminate cell type.
    4. Solid adenocarcinoma with mucin.
    5. Adenocarcinoma with mixed subtypes.
    6. Variants.
      1. Well-differentiated fetal adenocarcinoma.
      2. Mucinous (colloid) adenocarcinoma.
      3. Mucinous cystadenocarcinoma.
      4. Signet ring adenocarcinoma.
      5. Clear cell adenocarcinoma.
  3. Large cell carcinoma.
    1. Variants.
      1. Large cell neuroendocrine carcinoma (LCNEC).
      2. Combined LCNEC.
      3. Basaloid carcinoma.
      4. Lymphoepithelioma-like carcinoma.
      5. Clear cell carcinoma.
      6. Large cell carcinoma with rhabdoid phenotype.
  4. Adenosquamous carcinoma.
  5. Carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements.
    1. Carcinomas with spindle and/or giant cells.
    2. Spindle cell carcinoma.
    3. Giant cell carcinoma.
    4. Carcinosarcoma.
    5. Pulmonary blastoma.
  6. Carcinoid tumor.
    1. Typical carcinoid.
    2. Atypical carcinoid.
  7. Carcinomas of salivary gland type.
    1. Mucoepidermoid carcinoma.
    2. Adenoid cystic carcinoma.
    3. Others.
  8. Unclassified carcinoma.

Squamous cell carcinoma

Most squamous cell carcinomas of the lung are located centrally, in the larger bronchi of the lung. Squamous cell carcinomas are linked more strongly with smoking than other forms of NSCLC. The incidence of squamous cell carcinoma of the lung has been decreasing in recent years.


Adenocarcinoma is now the most common histologic subtype in many countries, and subclassification of adenocarcinoma is important. One of the biggest problems with lung adenocarcinomas is the frequent histologic heterogeneity. In fact, mixtures of adenocarcinoma histologic subtypes are more common than tumors consisting purely of a single pattern of acinar, papillary, bronchioloalveolar, and solid adenocarcinoma with mucin formation.

Criteria for the diagnosis of bronchioloalveolar carcinoma have varied widely in the past. The current WHO/IASLC definition is much more restrictive than that previously used by many pathologists because it is limited to only noninvasive tumors.

If stromal, vascular, or pleural invasion are identified in an adenocarcinoma that has an extensive bronchioloalveolar carcinoma component, the classification would be an adenocarcinoma of mixed subtype with predominant bronchioloalveolar pattern and a focal acinar, solid, or papillary pattern, depending on which pattern is seen in the invasive component. However, the future of bronchioloalveolar carcinoma as a distinct clinical entity is unclear; a multidisciplinary expert panel representing the IASLC, the American Thoracic Society, and the European Respiratory Society proposed a major revision of the classification of adenocarcinomas in 2011 that entails a reclassification of what was called bronchioloalveolar carcinoma into newly defined histologic subgroups.

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