Histology and epidemiological shift
It is reliably known that all types of lung cancer are closely associated with tobacco smoking. Nevertheless, about 15% of cases are registered in individuals who have never used tobacco.
Globally, two main pools are distinguished:
- Small cell lung cancer (SCLC).
- Non-small cell lung cancer (NSCLC).
Non-small cell lung cancer, in turn, is represented predominantly by adenocarcinoma and squamous cell carcinoma. Interestingly, about thirty years ago squamous cell type dominated, but now the ratio has shifted in favor of adenocarcinoma (1.4 to 1).
This phenomenon is explained by changes in tobacco product formats. The introduction of cigarettes with perforated filters and lower nicotine content ("light" cigarettes) forced smokers to take deeper puffs. The altered aerodynamics of the smoke flow led to the delivery of carcinogens to the distal airways, where adenocarcinoma forms. Nicotine itself is not a carcinogen, but it actively stimulates the growth of already established tumors.
Genetic markers and targeted therapy
Modern management protocols for patients with non-squamous cell carcinoma (primarily adenocarcinoma) require mandatory genetic testing. Identification of mutations allows for the prescription of highly effective oral tyrosine kinase inhibitors (TKIs).
Main molecular targets:
- EGFR (epidermal growth factor receptor). Mutations are common in the Asian population (up to 60%) and in women. Targeted drugs (afatinib, osimertinib) provide a pronounced response in 90% of patients. Survival reaches 3–4 years, but there is a high risk of brain metastases.
- KRAS. The most frequent aberration (~30% of adenocarcinomas). Typical for smokers and for the lepidic subtype in non-smokers. There are currently no drugs that reliably increase survival with this mutation; the prognosis remains poor.
- ALK (anaplastic lymphoma kinase). Gene rearrangements are characteristic of young patients with no smoking history. The disease runs an aggressive course with early CNS involvement (up to 40% at baseline). Newer generation drugs (alectinib, lorlatinib) cross the blood-brain barrier well, increasing median survival to 4.5 years.
- BRAF and ROS1. Rare mutations (1–2%) requiring specific inhibitor combinations (e.g., dabrafenib with trametinib for BRAF V600E).
Immunotherapy and PDL1 protein
Tumor cells are able to "evade" immune surveillance. They actively express the surface ligand PDL1, which binds to the PD1 receptor on T-lymphocytes, causing their exhaustion and suppressing the anti-tumor attack.
The use of immune checkpoint inhibitors (ICPIs, e.g., pembrolizumab) disrupts this bond, restoring the ability of T cells to destroy the tumor. If PDL1 expression on cells exceeds 50%, immunotherapy becomes the preferred choice, allowing for a median survival of about three years.
Tumor evolution and repeat biopsy
Malignant neoplasms exhibit high heterogeneity and the capacity for evolution during treatment. Targeted therapy creates selective pressure:
- New mutations: Clones of cells resistant to primary treatment emerge. For example, the EGFR T790M mutation renders the tumor resistant to first-generation drugs, but sensitive to osimertinib.
- Target loss: The tumor may lose its initial genetic aberration (transitioning to "wild type"), rendering inhibitors ineffective.
- Histological transformation: Non-small cell lung cancer can transform into small cell or squamous cell carcinoma.
This is why, upon clinical disease progression, routine repeat biopsy of new lesions has become the gold standard for adjusting the treatment regimen.
Environmental factors and the screening problem
In addition to active smoking, significant contributions to carcinogenesis are made by secondhand smoke (risk increases by 20–30%), air pollution with fine particulate matter less than 2.5 µm in diameter (diesel exhaust), and exposure to the radioactive gas radon (especially in miners).
Special attention should be given to asbestos (chrysotile fibers). Its combination with tobacco smoke has a powerful synergistic effect, increasing the probability of developing cancer by tens of times.
Regarding early detection, mass radiographic screening has proven ineffective. The large-scale Mayo Lung Project, comparing annual and more frequent (every 4 months) radiography, showed that although frequent screening allows for detecting tumors at earlier stages, it does not lead to an increase in overall survival for patients.
Briefly: answers to topical questions
What radiological signs are characteristic of peripheral lung cancer?
Peripheral lung cancer is characterized by the presence of a spherical or oval nodule, which is often an incidental finding. The main radiological signs include:
- Lobulation (lobulation) — a contour notch indicating uneven growth rates of tumor areas.
- Corona radiata sign (corona radiata) — numerous thin strands or spiculated margins radiating from the lesion.
- Dumbbell shape — or two nodules located close to each other.
- Calcification (calcification) — may be observed even in small peripheral tumors.
Also, superior sulcus tumors (Pancoast tumors) may visually resemble apical pleural thickening.
What chest CT changes indicate central lung cancer?
On CT, central lung cancer can present as an endobronchial lesion arising in a large bronchus at or near the lung hilum, and airway obstruction. Possible findings include:
- Lobar collapse (atelectasis) due to bronchial obstruction; on CT, the collapsed lobe forms an area of soft tissue density.
- Increased density in the right paramediastinal region with dense atelectasis of the right upper lobe, for example, in central bronchogenic carcinoma.
CT is significantly more sensitive than radiography for detecting obstructing carcinoma, especially if the endobronchial lesion is large enough to cause lobar collapse. However, the CT appearance lacks histological specificity and can be similar in bronchogenic carcinoma, endobronchial metastases, bronchial adenomas, and lymphoma.
Which groups of intrathoracic lymph nodes are evaluated in the radiological staging of lung cancer?
Radiological staging of lung cancer assesses lymph node involvement in the lung hilum and mediastinum. The following lymph node groups are evaluated:
- Hilar lymph nodes — bronchopulmonary and peribronchial (including ipsilateral).
- Mediastinal lymph nodes — paratracheal, subcarinal, aortopulmonary, subcarinal, and posterior mediastinal lymph nodes.
- Extrathoracic lymph nodes — supraclavicular and cervical lymph nodes (their ultrasound evaluation is recommended to increase the accuracy of preoperative staging).
Precise identification of involved groups is necessary to determine the potential resectability of the tumor.
What does the lepidic subtype of lung adenocarcinoma look like on computed tomography?
On computed tomography, the lepidic subtype of adenocarcinoma may appear as subsolid nodules or airspace opacification. Main CT features include:
- Subsolid nodules (subsolid nodules) — areas of ground-glass opacity that, in minimally invasive adenocarcinoma, typically contain a solid component of less than 5 mm.
- Pure ground-glass nodules (pure ground-glass nodules) — localized areas of increased density through which normal lung structures remain visible.
- Airspace opacification — focal or diffuse changes in the lung parenchyma.
The appearance of new solid components or an increase in existing ones within the nodule is considered a growth marker and requires further evaluation or treatment.
What is the role of PET-CT in the staging of non-small cell lung cancer?
The role of PET-CT in the staging of non-small cell lung cancer lies in the routine assessment of intrathoracic tumor extension. The method is used for:
- Lymph node assessment — determining tumor spread to the hylar and mediastinal lymph nodes.
- Increasing accuracy — 18F-FDG PET/CT demonstrates higher accuracy in detecting metastatic involvement compared to standalone CT, which has low specificity due to false-positive results in reactive hyperplasia.
- Determining treatment strategy — PET-CT results, combined with other methods, help answer key questions regarding tumor surgical resectability.
Class and exam questions
Is molecular genetic testing performed in small cell lung cancer?
No, biomarker testing (EGFR, ALK, etc.) is not routinely required in small cell lung cancer. It is mandatory for patients with stage 3 and 4 non-small cell lung cancer (predominantly adenocarcinomas).
Why has the epidemiology of histological subtypes changed?
The introduction of "light" filtered cigarettes forced smokers to inhale smoke more deeply. Carcinogens began to deposit in the distal parts of the lungs, leading to a sharp increase in the incidence of adenocarcinoma and a decrease in the proportion of squamous cell carcinoma.
How much does the risk decrease upon quitting tobacco?
Smoking cessation is most effective in reducing the risk of small cell and squamous cell carcinoma. Approximately 15 years after the last cigarette, the risk decreases by 50%.
What else to study on this topic
- Evaluation and differential diagnosis of solitary pulmonary nodules.
- Principles of lung cancer staging according to the 8th edition of the TNM classification.
- Benign lung neoplasms: hamartomas and their radiological features.
- Sarcomas and other rare primary malignant tumors of the respiratory system.
- Lymphangitic carcinomatosis and unusual patterns of pulmonary metastases.
Master the entire topic in the "Diagnostic Radiology" course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "Lung Neoplasms" and 2,199 more pages on the subject
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 10 video lessons on the subject
Other topics in the «Chest Radiology» section
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.