11. Bronchogenic Carcinoma

Bronchogenic Carcinoma • Lung cancer is the leading cause of cancer deaths in both men and women • The causal connection between cigarettes and lung cancer is now established not only epidemiologically but also through identification of carcinogens in tobacco smoke and analysis of the effect of these carcinogens on specific oncogenes expressed in lung cancer

Grey tumor arising in the main bronchus at a point of bifurcation. These tumors usually arise in the hilus or near the hilus of the lung

Bronchogenic squamous cell carcinoma arising in a left mainstem bronchus. Notice that the lung distal to this is atelectatic

Aetiology Cigarette smoking • Cigarette smoking causes more than 80% of cases of lung cancer • Through the 1990s, mortality from lung cancer fell among men while it increased among women, reflecting changing patterns of tobacco use over the past 30 years

Environmental risk factors • Exposure to environmental tobacco smoke • Radon gas (among uranium miners and in areas where radium in the soil causes significant indoor air contamination) • Asbestos (60- to 100-fold increased risk in smokers with asbestos exposure) • Metals (arsenic, chromium, nickel, iron oxide) • Industrial carcinogens (bis-chloromethyl ether) • Familial predisposition to lung cancer is recognized • Diseases associated with an increased risk of lung cancer, including pulmonary fibrosis, COPD, and sarcoidosis

Prognosis • The mean age at diagnosis of lung cancer is 60 • It is unusual under the age of 40 • After the diagnosis of lung cancer is made, approximately 40% of patients survive 1 year • The combined 5-year survival rate for all stages of lung cancer is now approximately 15%, improved from 12% in 1974–1976

Bronchogenic Carcinoma

Histologic types of bronchogenic carcinoma Squamous cell carcinoma (25– 35% of cases) • Arises from the bronchial epithelium, typically as a centrally located, intraluminal sessile or polypoid mass • Squamous cell tumors are more likely to present with hemoptysis and more frequently are diagnosed by sputum cytology • They spread locally and may be associated with hilar adenopathy and mediastinal widening on chest radiography

Squamous cell carcinoma

Squamous cell carcinoma

Adenocarcinoma (35–40% of cases) • Arises from mucus glands or, in the case of the bronchioloalveolar cell carcinoma (2% of cases), from any epithelial cell within or distal to the terminal bronchioles • Adenocarcinomas usually present as peripheral nodules or masses • Bronchioloalveolar cell carcinoma spreads intraalveolarly and may present as an infiltrate or as single or multiple pulmonary nodules.

Adenocarcinoma

Adenocarcinoma

Large cell carcinoma (5–10% of cases) • It is a heterogeneous group of relatively undifferentiated tumors that share large cells and do not fit into other categories • Large cell carcinomas typically have rapid doubling times and an aggressive clinical course • They present as central or peripheral masses.

Large cell carcinoma

Small cell carcinoma (15–20% of cases) • It is a tumor of bronchial origin that typically begins centrally, infiltrating submucosally to cause narrowing or obstruction of the bronchus without a discrete luminal mass • Hilar and mediastinal abnormalities are common on chest radiography

Small cell carcinoma

Small cell lung cancer

• For purposes of staging and treatment, bronchogenic carcinoma is divided into small cell lung cancer (SCLC) and the other three types, conveniently labeled non– small cell lung cancer (NSCLC) • This practical classification reflects different natural histories and different treatment SCLC • SCLC is prone to early hematogenous spread • It is rarely amenable to surgical resection and has a very aggressive course with a median survival (untreated) of 6–18 weeks NSCLC • The three histologic categories comprising NSCLC spread more slowly • They may be cured in the early stages following resection, and they respond similarly to chemotherapy

Clinical Findings Lung cancer is symptomatic at diagnosis in 75–90% of patients The clinical presentation depends on the type and location of the primary tumor, the extent of local spread, and the presence of distant metastases and any paraneoplastic syndromes

Symptoms

• Anorexia, weight loss, or asthenia occurs in 55– 90% of patients presenting with a new diagnosis of lung cancer Cough: • Up to 60% of patients have a new cough or a change in a chronic cough. It may be dry or purulent sputum is present if secondary infection Hemoptysis: • Common if tumour is in central bonchus • Repeated scanty hemoptysis or blood streaked sputum in a smoker is highly suggestive

Pancoast’s syndrome: • Featured by pain in shoulder and inner aspect of the arm • Caused by involvement of lower part of brachial plexus

Dysphagia: • Mediatinal spread may lead to dysphagia

Symptoms due to blood borne metastasis: • • • • • •

Focal neurologocal defecits Epileptic seizures Personality change Jaundice Bone pain Skin nodules

Hoarsness: Compromise of the recurrent laryngeal nerve

Superior vena cava syndrome obstruction of the superior vena cava with supraclavicular venous engorgement

57 yr old male who presented with hemoptysis and radicular left arm pain. Note typical Horner’s syndrome.  Bronchogenic carcinoma or Pancoast tumour was etiology

Paraneoplastic understood patterns of organ • They are incompletely Syndrome dysfunction related to immune-mediated or secretory effects of neoplasms

• Patients with small cell carcinoma can develop syndrome of inappropriate antidiuretic hormone (SIADH) • Squamous cell carcinoma can develop hypercalcemia due to secretion of PTH-like peptide • Digital clubbing is seen in up to 20% of patients at diagnosis • Other common paraneoplastic syndromes include increased ACTH production, anemia, hypercoagulability, peripheral neuropathy, and the Eaton-Lambert myasthenia syndrome • Their recognition is important because treatment of the primary tumor may improve or resolve symptoms even when the cancer is not curable

Signs Examination is normal unless the disease is far advanced Bronchial obstruction: • • • •

Signs of Signs of Signs of Wheeze

collapse obstructive emphysema pneumonia which fails to clear after coughing

Phrenic nerve paralysis: • Signs of unilateral diaphragmatic palsy

Pleural involvement • Pleural rub and signs of pleural effusion

Digital Clubbing: • Associated with Hypertrophic pulmonary oteoarthropathy (HPOA), giving rise to pain and tenderness due to periostitis of long bones

Investigations Laboratory Findings • The diagnosis of lung cancer rests on examination of a tissue or cytology specimen

Sputum cytology • It is highly specific but insensitive; the yield is highest when there are lesions in the central airways

Thoracentesis • Used to establish a diagnosis of lung cancer in patients with malignant pleural effusions • If cytologic examination of an adequate sample (50–100 mL) of pleural fluid is nondiagnostic, the procedure should be repeated once. If results remain negative, thoracoscopy is preferred to blind pleural biopsy

Fine-needle aspiration • FNA of palpable supraclavicular or cervical lymph nodes is frequently diagnostic

Fiberoptic bronchoscopy: • It allows visualization of the major airways • Cytology brushing of visible lesions and lavage of lung segments with cytologic evaluation of specimens • Direct biopsy of endobronchial abnormalities • Blind transbronchial biopsy of the pulmonary parenchyma or peripheral nodules • Fine-needle aspiration biopsy of mediastinal lymph nodes

Imaging • Nearly all patients with lung cancer have abnormal findings on chest radiography or CT scan • Following are some of the finding but they are rarely specific for a particular diagnosis Unilateral Hilar enlargement Peripheral pulmonary opacity Lung lobe or segmental collapse Pleural effusion Broadening of mediastinum, enlarged cardiac shadow, elevation of hemidiaphragm • Rib destruction • • • • •

The patient's PA chest x-ray showing the tumor in the posterior mediasinum

PA chest X-ray reveals a large suprahilar density. There is bilateral pleural thickening, with calcification

Small Cell Carcinoma

A large central lesion was diagnosed as non– small cell carcinoma

Left pleural effusion and volume loss secondary to non–small cell carcinoma of the left lower lobe. The pleural effusion was found to be malignant; therefore, the lesion is inoperable

Complete left lung collapse secondary to bronchogenic carcinoma of left mainstem bronchus

Peripheral pulmonary carcinoma

Staging • Accurate staging is crucial: • (1) to provide the clinician with information to guide treatment • (2) to provide the patient with accurate information regarding prognosis • (3) to standardize entry criteria for clinical trials to allow interpretation of results

Staging of NSCLC • The TNM international staging system attempts a physical description of the neoplasm • Primary Tumor (T): T describes the size and location of the primary tumor

• Regional Lymph Nodes (N) N describes the presence and location of nodal metastases

• Distant Metastases (M)  M refers to the presence or absence of distant metastases

• This classification is used to guide therapy • Many patients with stage I and stage II disease are cured through surgery • Patients with stage IIIB and stage IV disease do not benefit from surgery • Patients with stage IIIA disease have locally invasive disease that may benefit from surgery in certain circumstances.

Staging of SCLC • SCLC is not staged using the TNM system because micrometastases are assumed to be present on diagnosis • SCLC is divided into two categories: • Limited disease (30%), when the tumor is limited to the unilateral hemithorax (including contralateral mediastinal nodes); • Extensive disease (70%), when the tumor extends beyond the hemithorax (including pleural effusion) • This scheme also guides therapy • Patients with limited SCLC benefit from thoracic radiation therapy in addition to chemotherapy and may benefit from prophylactic cranial radiation therapy

Treatment Non–Small Cell Carcinoma Surgical Resection: • Cure of NSCLC is unlikely without resection • Initial approach to the patient is determined by the answers to two questions: • (1) Is complete surgical resection technically feasible? • (2) If yes, is the patient able to tolerate the surgery with acceptable morbidity and mortality? • Radiation therapy following surgery improves local control but does not improve survival.

Contraindications to surgical resection • Extrathoracic metastases • Malignant pleural effusion • Tumor involving the heart, pericardium, great vessels, esophagus, recurrent laryngeal or phrenic nerves, trachea, main carina, or contralateral mediastinal lymph nodes

Neoadjuvant chemotherapy • It consists of giving antineoplastic drugs in advance of surgery or radiation therapy • There is no consensus on the impact of neoadjuvant therapy on survival • Neoadjuvant therapy is more widely used in selected patients

Adjuvant chemotherapy • It consists of administering antineoplastic drugs following surgery or radiation therapy • Adjuvant chemotherapy with alkylating agents such as cyclophosphamide increases mortality so it is not recommended. Newer antineoplastic agents with less toxicity are in clinical trials in these patients • Chemotherapy in NSCLC is not very effective • Multidrug platinum-based chemotherapy is associated with an increase in survival in patients with advanced disease There is no evidence of a survival benefit in patients with poor performance status

Treatment Small Cell Carcinoma Chemotherapy Response rates of SCLC to cisplatin and etoposide are excellent: • 80–100% response in limited-stage disease • 60–80% response in extensive stage disease • However, remissions tend to be short-lived with a median duration of 6–8 months • Once the disease has recurred, median survival is 3–4 months • Overall 2-year survival is 20% in limited-stage disease and 5% in extensive-stage disease

Radiation therapy Thoracic radiation therapy improves survival in patients with limited SCLC but not those with extensive disease Whole brain radiation therapy decreases the incidence of central nervous system disease but does not affect survival

Palliative therapy

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Radiotherapy: External beam radiation therapy is used to control dyspnea and hemoptysis, pain from bony metastases, obstruction from superior vena cava syndrome, and symptomatic brain metastases Intraluminal radiation (brachytherapy) is an alternative approach to endobronchial disease. • Photoresection with the Nd:YAG laser It is sometimes performed on central tumors to relieve endobronchial obstruction, improve dyspnea, and control hemoptysis Resection Resection of solitary brain metastases does not affect survival but may improve quality of life when combined with radiation therapy Pain control • As patients approach the end of life, meticulous efforts at pain control are essential Consultation with a palliative care specialist

Prognosis • The overall 5-year survival rate for lung cancer is 15% • Predictors of survival are the type of tumor (SCLC versus NSCLC), the stage of the tumor, and the patient's performance status, including weight loss in the past 6 months • Best prognosis is with well-differentiated Squamous cell tumors which have not metastasized and are amenable to surgical resection

Rarer Types of Lung Tumors • Adeno-squamous carcinoma • Carcinoid tumor • Bronchial gland adenoma • Bronchial gland carcinoma • Hamartoma • Bronchioalveolar Carcinoma