creation date: 2025-10-30 18:19
tags: Pathologies
Lung Cancer
Background
Definitions
Lung cancer, also referred to as bronchogenic carcinoma, refers to tumours originating in the lung parenchyma or within the bronchi.
Etiology
Smoking is the leading cause of lung cancer with 90% of cases attributable to smoking.
Other carinogens include:
- Asbestos (especially occupational exposure) - associated with mesothelioma
- Radon (from uranium decay)
- Radiation for non-lung cancer treatment (eg. non-Hodgekins lymphoma, breast cancer)
- Metals (eg. chromium, nickel, arsenic) and polycyclic aromatic hydrocarbons
Other factors include:
- Environmental and genetic components
- Idiopathic pulmonary fibrosis
Pathogenesis
The exact mechanisms are incompletely understood but generally thought to be as follows:
- Repeated exposure of carcinogens leads to dysplasia of lung epithelium
- Continued exposure results in genetic mutations
- Mutations disrupt cell cycle and promotes carcinogenesis
The most common genetic mutations responsible are MYC, BCL2, and p53 for small cell lung cancer and EGFR, KRAS, and p16 for non-small cell lung cancer.
Non-Small Cell Lung Cancer (NSCLC) accounts for 80-85% of cases. Major subtypes are differentiated by histology:
- Adenocarcinoma: outer part of lungs, originating from the glandular cells that produce mucus; associated with genetic mutations (and not linked to smoking) and appears as pneumonia on CXR. This is the most common form of lung cancer.
- Squamous cell carcinoma: central parts of the lungs near bronchi, originating from squamous epithelial cells lining the airway; associated with smokers and produces PTHrP (which can result in hypercalcemia)
- Large cell carcinoma: heterogenous group characterized by large, abnormal cells that does not have features of other types - diagnosis of exclusion
- Other variants are rare but includes adenosquamous carcinoma, sarcomatoid carcinoma, and bronchial carcinoids carcinoma
Small Cell Lung Cancer (SCLC) accounts for the remaining 15% of lung cancers and is characterized by small immature neuroendocrine cells that multiply rapidly to form large tumours. The neuroendocrine nature results in a number of paraneoplastic symptoms (eg. SIADH, Cushing’s syndrome, Lambert-Eaton syndrome). Variants consist of:
- Pure small cell carcinoma: classic form made entirely of small cells
- Combined small cell carcinoma: both small cell carcinoma and components of NSCLC cells
Clinical Presentation
Signs & Symptoms
Lung cancer may present as suggestive symptoms:
- Cough
- Hemoptysis
- Dyspnea
- Wheezing
- Dysphagia
- Hoarseness
It may also be an incidental or screening finding on imaging on an asymptomatic patient.
Symptoms of metastatic disease vary based on site of metastasis. Common sites are:
- Brain (headache, seizure, focal deficits)
- Bone (pain, pathologic fracture, spinal cord compression)
- Liver (asymptomatic or RUQ pain, liver enzyme abnormalities, jaundice)
- Adrenals (asymptomatic or constitutional symptoms possible)
Suspicious imaging features include:
- Lesions >3 cm that are new
- Measurable growth in any nodule or mass
- Pleural nodularity
- Asymmetric or significantly enlarged hilar or paratracheal nodes
- Endobronchial lesion
- Consolidation thought to be pneumonia that fails to resolve with medical management
Concerning but less specific findings include:
- Pleural effusions
- Non-dependent or substantial atelectasis
- Pleural plaques (indicating significant asbestos exposure)
Features on chest CT that may suggest malignancy include:
- Lesions with irregular or spiculated border (due to vascularization)
- Thick-walled cavitary lesions (especially when not in active infection)
- Nodule with mixed attenuation, containing a solid and a less dense ground-glass component
- Pure ground-glass lesions
- Multiple nodules (may be metastases)
History & Physical Exam
History should evaluate for risk factors of malignancy. This includes:
- Age
- Sex (male more likely)
- Family history
- Presence of emphysema
Suspicion of lung cancer should prompt thorough history and physical with particular focus on nonpulmonary symptoms that might suggest metastases. This includes:
- Constitutional symptoms
- MSK pain
- Neurologic symptoms and altered mental status recently
- Lymphadenopathy
- Hoarseness, SVC syndrome
- Bone tenderness
- Hepatomegaly
- Focal neurologic signs
- Papilledema
- Soft tissue mass
Risk factors
- Smoking history
- Exposures
- Family history
Diagnosis
Criteria
Definitive diagnosis of lung cancer is made with pathology. This involves tissue biopsy (most often with percutaneous CT-guided biopsy or bronchoscopy) or cytologic sample (eg. needle aspirates).
Microscopy and staining will differentiate between the types of lung cancer.
Work-up
Suspected lung cancer
Following suspicion and/or initial incidental imaging findings. The patient should undergo contrast-enhanced CT chest. A stand-alone CT is indicated even if PET/CT is planned (PET/CT is without contrast and lower resolution).
Chest CT is used for:
- TNM staging
- Associated lung conditions
- Planning of biopsy site(s)
Following preliminary findings, additional imaging may be indicated for assessment of metastases. This includes clinically-directed CT imaging (low sensitivity) or whole-body PET/CT (high false-positive rate). This is typically suggested when there is a high likelihood of extensive disease.
Age-related cancer screening
Due to the possibility of an alternative primary malignancy resulting in metastases to the lungs. Specific cancer screening should be done based on risk factors.
Screening
In Ontario, the Ontario Lung Screening Program (OLSP) is a screening program for people at high risk of getting lung cancer. This eligibility requirements are as follows:
- Age 55-80 years old
- Have smoked daily for at least 20 years (cumulatively, not necessarily consecutively)
- Has OHIP coverage
Patients can either be assessed for eligibility through a physician or through self-referral to the program.
The screening consist of a one-time low-dose CT scan.
Differential
Primary lung cancer is less likely than metastases to the lungs. As such it is important to rule out alternative malignancies (eg. breast cancer, colon cancer, prostate cancer).
Alternative diagnoses that may present similarly or appear similarly on chest x-ray include:
- Bacterial pneumonia
- Bronchitis
- Mycoplasmal pneumonia
- Pleural effusion
- Pneumothorax
- Tuberculosis
- Viral pneumonia
- Fungal pneumonia
Red Flags / Complications
Prognosis of NSCLC typically correlates with TNM staging. Prognosis of SCLC are poor, with limited-stage disease having a 5-year survival of 10-13% and extensive-stage disease of 1-2%.
Complications seen in patients undergoing treatment include:
- Chemotherapy-induced nausea and vomiting
- Fatigue
- Anorexia
- Weight loss
- Anemia
- Neutropenia
- Nephrotoxicity
- Neurotoxicities
Management
Non-Small Cell Lung Cancer
The treatment modality for NSCLC depends on the staging of the disease. This includes:
- Surgery alone (stage I)
- Surgery with adjuvant chemotherapy (stage II-III)
- Surgery with chemotherapy in addition to targeted radiotherapy based on tolerance and extent of involvement (stage III)
With stage IV disease, treatment is not considered curative and aims to improve survival and alleviating symptoms.
Non-squamous NSCLC without brain metastasis or hemoptysis may benefit from bevacizumab.
For cancers with specific mutations, targeted therapy is also available. It is currently routine to check for these in every advanced NSCLC:
- EGFR (epidermal growth factor receptor) - target with tyrosine kinase inhibitors
- ALK (anaplastic lymphoma kinase) - target with inhibitors crizotinib, ceritinib, or alectinib
Immunotherapy may also be available for certain forms of NSCLC.
Small Cell Lung Cancer
SCLC is sensitive to chemotherapy and is the primary treatment modality. Radiotherapy and immunotherapy may be considered in some cases.
It should be noted that SCLC has a high recurrence rate. However, in patients who achieve remission, prophylactic whole brain radiation is done to reduce symptomatic brain metastasis.