What are the main types of lung cancer, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC)?

Main Types of Lung Cancer

The two main types of lung cancer are non-small cell lung cancer (NSCLC), which accounts for 80-85% of cases, and small cell lung cancer (SCLC), which represents 15-20% of cases. 1

Non-Small Cell Lung Cancer (NSCLC)

NSCLC represents more than 80% of all lung cancer cases and is further divided into distinct histological subtypes with different clinical behaviors 1:

Major NSCLC Subtypes

• Adenocarcinoma: Comprises approximately 40% of all lung cancers and is the most common NSCLC subtype 1

  • Typically presents as peripheral lesions originating in the bronchioles terminales and respiratory bronchioles 2
  • Characterized by glandular or acinar differentiation with cells showing moderate cytoplasm, vesicular chromatin, and prominent nucleoli 2
  • Immunohistochemically positive for TTF-1 and napsin A 2
  • More common in never-smokers and women compared to other lung cancer types 1

• Squamous Cell (Epidermoid) Carcinoma: Accounts for approximately 30% of lung cancers 1

  • Generally presents as central/endobronchial lesions 2
  • Histologically shows intercellular bridges, keratinization, and keratin pearl formation 2
  • Immunohistochemically positive for p63 and cytokeratins 5/6, typically negative for TTF-1 2

• Large Cell Carcinoma: Represents 5-10% of NSCLC cases 1

Important Clinical Distinction

The historical grouping of these cancers under "NSCLC" is increasingly recognized as problematic, as adenocarcinoma and squamous cell carcinoma are vastly distinct diseases at molecular, pathological, and clinical levels, with different genetic drivers, prognostic profiles, and treatment responses 3. Specific subtyping is now mandatory for therapeutic decision-making 1.

Small Cell Lung Cancer (SCLC)

SCLC represents fewer than 20% of lung cancers but has distinct aggressive characteristics 1:

Key Features

• Presentation: Typically presents as a large hilar mass (85%) with bulky mediastinal adenopathy (75%), causing peribronchial compression and obstruction 2
• Metastatic behavior: Approximately 66-70% of patients present with metastatic disease at diagnosis 1, 2
• Histology: Small cells with scant cytoplasm, poorly defined cell borders, finely granular nuclear chromatin, absent or inconspicuous nucleoli, high mitotic count, and characteristic crushing artifact 2
• Paraneoplastic syndromes: More frequent than in NSCLC, including Lambert-Eaton syndrome, paraneoplastic encephalomyelitis, sensory neuropathy, and syndrome of inappropriate ADH secretion 2
• Smoking association: Nearly all cases are attributable to cigarette smoking 1

Staging Approach

SCLC is commonly classified into two clinical stages based on radiation therapy field inclusion 1:

• Limited stage: Typically includes TNM stage I-III
• Extensive stage: Includes TNM stage IV (metastases) or tumor/nodal volume too extensive for tolerable radiation planning

Critical Prognostic Differences

The distinction between these types has profound implications for survival 4:

• Early-stage NSCLC (Stage I): 5-year survival rates up to 70% with surgical resection
• Advanced NSCLC (Stage IV): 1-year survival only 15-19%
• SCLC: Highly aggressive with early metastases and poor prognosis despite initial chemosensitivity 2