Main Types of Lung Cancer: Histological
Features, Prognosis, and Treatment
Strategies
Introduction
Lung cancer is the most common cause of cancer-related mortality globally among both
men and women. Although rare below the age of 40, its incidence increases sharply with
age. The projected lifetime risk of developing lung cancer is approximately 8% in males
and 6% in females. Smoking remains the principal risk factor, contributing to 80–90% of
all lung cancers, while other factors such as environmental exposures, genetic mutations,
and prior lung diseases also play significant roles.
Histologically, lung cancers are classified based on cellular morphology and origin.
These classifications aid in predicting the clinical course and guiding management
strategies. The primary types of lung cancer include small cell and non-small cell
carcinomas, with further subtypes and rarer tumor variants grouped accordingly.
Classification of Lung Cancer
Lung cancers are classified into the following major categories:
1. Non-Small Cell Lung Cancer (NSCLC)
- Adenocarcinoma
- Squamous Cell Carcinoma
- Large Cell Carcinoma
2. Small Cell Lung Cancer (SCLC)
3. Other Types
- Undifferentiated carcinomas
- Carcinoid tumors
- Bronchial gland tumors (e.g., adenoid cystic carcinoma, mucoepidermoid carcinoma)
- Rare tumor types
Note: The focus of this response is on the first two major types: NSCLC and SCLC.
1. Non-Small Cell Lung Cancer (NSCLC)
NSCLC accounts for approximately 75–80% of all lung cancers. It is further subdivided
into adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. These tumors
generally exhibit slower growth and spread compared to small cell lung cancer.
a. Adenocarcinoma
Histological Features:
Displays glandular differentiation and mucin production. It commonly arises in the
peripheral regions of the lungs and may present as a solitary mass or diffuse nodular
pattern. The bronchioloalveolar subtype can mimic pneumonia radiologically.
Epidemiology and Associations:
Most common subtype in non-smokers and women. Frequently occurs in areas of prior
fibrosis or scarring.
Prognosis:
Prognosis is generally favorable in early-stage disease and improves further with the
presence of targetable mutations (e.g., EGFR, ALK).
Treatment Strategies:
- Surgery: Primary option in early-stage localized disease.
- Targeted Therapy: For patients with driver mutations (e.g., EGFR, ALK, ROS1).
- Immunotherapy/Chemotherapy: Used in advanced cases or in patients without
targetable mutations.
b. Squamous Cell Carcinoma
Histological Features:
Characterized by keratin pearls and intercellular bridges. Typically located centrally in
the lung and may cavitate.
Epidemiology and Associations:
Strongly associated with tobacco smoking. Classically associated with hypercalcemia due
to parathyroid hormone-related protein (PTHrP) secretion.
Prognosis:
Intermediate prognosis; better than large cell carcinoma but often diagnosed at a locally
advanced stage.
Treatment Strategies:
- Surgery: Considered for resectable disease.
- Chemoradiotherapy: Used in non-operable or advanced disease.
c. Large Cell Carcinoma
Histological Features:
Poorly differentiated neoplasm with large polygonal cells and no features of
adenocarcinoma or squamous differentiation.
Epidemiology:
Typically arises peripherally in the lung.
Prognosis and Treatment:
Often presents late and has a poor prognosis. Managed similarly to other NSCLC
subtypes with surgery, chemotherapy, and immunotherapy as appropriate.
2. Small Cell Lung Cancer (SCLC)
SCLC comprises about 20–30% of all lung cancers and is known for its aggressive
clinical course and early metastasis.
Histological Features:
Composed of small cells with scant cytoplasm, fine chromatin, and high mitotic activity.
Typically shows neuroendocrine differentiation.
Epidemiology and Associations:
Strongly linked to heavy cigarette smoking. Most cases present with widespread disease
at the time of diagnosis. Associated with paraneoplastic syndromes such as SIADH,
ectopic ACTH production, and neurologic syndromes (e.g., Lambert-Eaton myasthenic
syndrome).
Prognosis:
Extremely poor without treatment, with a median survival of about 3 months. With
therapy, survival may extend to 1–1.5 years.
Treatment Strategies:
- Surgery: Rarely indicated due to early dissemination.
- Chemotherapy and Radiotherapy: Mainstay of treatment.
- Limited-stage disease: Treated with combination chemotherapy (e.g., cisplatin +
etoposide) and concurrent thoracic radiotherapy.
- Extensive-stage disease: Treated with systemic chemotherapy alone.
- Prophylactic Cranial Irradiation (PCI): Often used to prevent brain metastasis.
Comparison of NSCLC and SCLC
Feature | NSCLC | SCLC
-------------------------------|----------------------------------------------|-----------------------------
----------------
Prevalence | ~75–80% of lung cancers | ~20–30% of lung
cancers
Growth and Spread | Slower progression, later metastasis | Rapid
progression, early widespread metastasis
Common Subtypes | Adenocarcinoma, squamous, large cell | Pure SCLC,
neuroendocrine subtypes
Paraneoplastic Syndromes | Less common | Frequently associated
Surgery Role | Often applicable in early-stage disease | Rarely indicated
Chemotherapy | Used in advanced stages | Mainstay of therapy
Targeted Therapy | Effective in mutation-positive adenocarcinoma | Limited role
Prognosis | ~50% 2-year survival (localized), ~10% with spread | Median 1–
1.5 years with treatment
Conclusion
The classification of lung cancers into NSCLC and SCLC plays a critical role in
diagnosis, prognosis, and treatment planning. While NSCLC is more common and often
amenable to surgical intervention and targeted therapies, SCLC presents with a more
aggressive course and is primarily managed with systemic therapy. A multidisciplinary
approach is essential in the management of both types, and ongoing advancements in
molecular diagnostics and immunotherapy are continuously improving patient outcomes.
