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Bronchogenic carcinoma, simply called lung cancer, is a malignant tumor arising from the epithelial lining of the bronchus or bronchiole.
Epidemiology and Etiology of Bronchogenic Carcinoma
The incidence of bronchogenic carcinoma is estimated to be more than 200,000 cases per year making it the second most common malignancy in the United States, after prostate cancer in men and breast cancer in women. Mortality-wise, it causes the highest cancer-related deaths in the United States, about 160,000 deaths per year in the United States are related to bronchogenic carcinoma. The average age at the time of diagnosis is around 65 years.
Tobacco smoking is the single most important etiologic risk factor for the bronchogenic carcinoma. The risk of bronchogenic carcinoma has a direct relationship with the duration and dose of tobacco smoking. The passive (second-hand) smoking is also a risk factor.
The other known risk factors for bronchogenic carcinoma are exposure to asbestos, radon, arsenic, beryllium, chromium, nickel and soot.
Classification of Bronchogenic Carcinoma
The bronchogenic carcinoma is histologically divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with the latter further divided into three main subtypes i.e. squamous-cell carcinoma, adenocarcinoma, and large-cell carcinoma.
- Adenocarcinoma is the most common type of all bronchogenic carcinomas representing about 35–40 % of the bronchogenic carcinomas. It is more common in women and in nonsmokers. Adenocarcinoma is peripherally located and histologically contains glands.
- Squamous cell carcinoma is strongly associated with a history of tobacco smoking and is usually located in the center of the lungs. It is associated with cavitation and PTH related protein secretion.
- Large-cell carcinoma is peripherally located and is undifferentiated histologically. The cells do not show gland formation as is the case with adenocarcinoma or keratinization as is found in squamous cell carcinoma. It is related to tobacco smoking and has a poor prognosis.
- Small-cell carcinoma is a central tumor and is more common in smokers. It is a very aggressive form of bronchogenic carcinoma. These tumors are more likely to metastasize to distant organs at the time of presentation and the prognosis is usually grim. They originate from Kluchtisky (neuroendocrine) cells.They may be associated with paraneoplastic syndromes (Lambert-Eaton syndrome, ectopic secretion of ADH or ACTH),
Clinical Presentation of Bronchogenic Carcinoma
The clinical presentation of bronchogenic carcinoma depends on the location of the tumor and the histological type. Approximately 10% of patients are asymptomatic and the bronchogenic carcinoma is detected on chest radiographs done for other reasons.
A cough is the most common presenting symptom; hence any change in the character or severity of a cough in a smoker is always a red alarm for a possible lung cancer. Due to the overlap between the symptoms and risk factors of chronic obstructive lung disease and bronchogenic carcinoma, the threshold to suspect lung cancer should always be low in a smoker.
Patients may also complain of anorexia, weight loss, chest pain or discomfort, shortness of breath and hemoptysis. Secondary bacterial infections of the lung can also be a presentation of bronchogenic carcinoma.
In metastatic bronchogenic carcinoma, the clinical features of the involved organs are also present. For instance, seizures, headache, personality changes, bone pain, abdominal pain, and jaundice. The common metastatic sites include lymph nodes, bones, liver, central nervous system (brain and spinal cord), and adrenal glands.
Paraneoplastic syndromes are usually identified in bronchogenic carcinoma and each presentation can be clearly linked to certain histological subtypes. For instance,
- Hypercalcemia is more common with squamous cell carcinoma due to ectopic secretion of the parathyroid hormone related peptide (PTHrP).
- Endocrine syndromes, such as syndrome of inappropriate secretion of antidiuretic hormone (SIADH), ectopic ACTH production and Eaton-Lambert-Eaton syndrome are associated with small-cell lung cancer.
- Finger clubbing (hypertrophic osteoarthropathy) can be found in all types of bronchogenic carcinoma.
Physical examination may be normal or may reveal
- Anemia, finger clubbing, enlarged lymph nodes
- Decreased breath sounds due to underlying malignant pleural effusion
- Wheezes due to accompanying COPD
- Facial swelling, plethora, dilated vessels and upper limb edema due to superior vena cava syndrome
- Hoarseness due to recurrent laryngeal nerve palsy
- Ptosis, miosis, and facial anhidrosis due to Horner syndrome (Pancoast tumor)
Diagnostic Workup and Staging of Bronchogenic Carcinoma
A chest radiograph is the first step in a patient suspected with bronchogenic carcinoma. Any known smoker, who presents with a recent-onset cough, or a change in their cough and respiratory function, should have a chest x-ray.
If the chest x-ray reveals a nodule, it should always be compared with a previous (old) chest x-ray, if available.
It should be noted that a normal chest radiograph does not exclude lung cancer because a small tumor can be hidden within the mediastinum or elsewhere in the chest. If the suspicion of bronchogenic carcinoma is high on the basis of history and physical examination, then further imaging with CT scan and PET scan are advised.
The next diagnostic step depends upon the location of the nodule.
- For central nodules, sputum cytology can be useful to aid with the diagnosis as it can reveal malignant cells. Bronchoscopic and transthoracic biopsies are indicated to define the histological type of the bronchogenic carcinoma, as this clearly affects the treatment plan and prognosis.
- For peripheral nodules, CT guided transthoracic biopsy is indicated to identify the histological type of cancer.
The routine laboratory investigations in lung cancer can reveal hypercalcemia, hypophosphatemia, hyponatremia (due to SIADH), or increased ACTH.
Computerized tomography of the chest is used for staging purposes. A CT scan can also help to differentiate between small and non-small cell lung cancer, as the former is more commonly associated with massive lymphadenopathy.
Positron emission tomography (PET) scan is commonly used in patients with bronchogenic carcinoma to identify possible mediastinal involvement and distant metastasis.
After confirmation of the histological diagnosis, a detailed staging work-up should be performed to determine the extent of disease, the presence of distant metastasis and to identify potential candidates for surgery.
The TNM (tumor-nodes-metastasis) system is used for the staging of the bronchogenic carcinoma.
Treatment of Bronchogenic Carcinoma
The management plan of bronchogenic carcinoma is based on its histology, staging, location, and co-morbid of the patient. The available treatment options are evolving and complex, and in broad terms include surgery, radiotherapy, and chemotherapy.
Generally, there are different treatment options for patients with SCLC and NSCLC.
In early stages of NSCLC, the surgical resection of the tumor is indicated as an intent-to-cure therapy.
In late stages, a multidisciplinary approach is often indicated along with chemotherapy and radiotherapy.
The palliative care should be initiated early in patients with metastatic disease, or if underlying morbidity of patient prevents potentially curable therapy. It improves quality of life.
Since most of the SCLCs have been metastasized at the time of diagnosis, the surgical treatment option is often not feasible. Although surgery can be done in the rare case when SCLC is localized to the lungs.
The chemotherapy and radiotherapy should be pursued but has limited success. The five-year survival rate is virtually zero for extensive stage SCLC.
Similar to the NSCLC, the palliative care should be initiated early to improve the quality of life.