What are the types of lung cancer?

Types of Lung Cancer

Lung cancer is primarily divided into two major classes based on biology, therapy, and prognosis: Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC). 1

Non-Small Cell Lung Cancer (NSCLC)

NSCLC accounts for more than 85% of all lung cancer cases and includes two major types:

1. Nonsquamous carcinoma:

   • Adenocarcinoma (40-50% of all lung cancers)
   • Large-cell carcinoma (5-10%)
   • Other cell types

2. Squamous cell (epidermoid) carcinoma (20-30% of all lung cancers)

Adenocarcinoma

• Most common type of lung cancer in the United States
• Most frequently occurring cell type in nonsmokers 1
• Current classification includes:
  • Adenocarcinoma in situ (AIS) - preinvasive lesion
  • Minimally invasive adenocarcinoma (MIA)
  • Invasive adenocarcinoma
  • Variants of invasive adenocarcinoma 1

Squamous Cell Carcinoma

• More often presents as central endobronchial lesions
• Strongly associated with smoking history
• Rarely harbors EGFR mutations or EML4-ALK rearrangements 1

Large-Cell Carcinoma

• Tends to arise in the lung periphery
• Often invades the pleura
• Diagnosis of exclusion when the tumor lacks features of adenocarcinoma or squamous differentiation

Small Cell Lung Cancer (SCLC)

SCLC represents approximately 15% of all lung cancers 1:

• Nearly all cases are attributable to cigarette smoking
• Characterized by rapid growth and early metastasis
• Commonly classified into two clinical stages:
  1. Limited stage (typically includes TNM stage I to III)
  2. Extensive stage (includes TNM stage IV and extensive tumor/nodal volume) 1
• Approximately 66% of SCLC cases present with metastatic disease at diagnosis 1

Molecular and Genetic Characteristics

NSCLC Molecular Features

• Adenocarcinoma: Often harbors EGFR mutations, EML4-ALK rearrangements, KRAS mutations, MET amplification, and ROS1/RET rearrangements 1, 2
• Squamous Cell Carcinoma: Often shows alterations in RTKs, DDR2, FGFR1, FGFR3, and inactivating mutations in CDKN2A, PTEN, and other genes 1, 2

SCLC Molecular Features

• Frequently shows MYC amplification
• JAK-STAT pathway activation is common 2

Prognostic Factors

Good prognostic factors for NSCLC include:

• Early-stage disease at diagnosis
• Good performance status (ECOG 0,1, or 2)
• No significant weight loss (not > 5%)
• Female sex 1

Clinical Implications

The classification of lung cancer is critical for:

1. Determining appropriate treatment strategies
2. Predicting response to targeted therapies
3. Guiding molecular testing (e.g., EGFR, ALK, ROS1, PD-L1)
4. Estimating prognosis

The WHO classification and accurate subtyping are essential for selecting appropriate therapy, as treatment options increasingly depend on specific histologic and molecular characteristics rather than just broadly categorizing tumors as NSCLC or SCLC 1.