Definition
Bronchogenic carcinoma is a malignant neoplasm of the lung arising from the epithelium of the bronchus or bronchiole.

Incidence

Accounts for 14% of all new cancers in males and 13% of all new cancers in females.

Seventy percent of all lung cancer deaths occur between the ages of 55 and 74. However, recent trends indicate that both the incidence and mortality of lung cancer is increasing in younger age groups.

It is approximately three times more common in men than females. However the incidence of lung cancer in females in increasing in epidemic proportions.

Lung cancer leads as cause of cancer deaths among women and men.

The countries with the highest incidence of lung cancer among males is the United Kingdom

In general, the incidence of lung cancer in industrialized western countries is increased compared to third world countries.

The highest incidence of lung cancer in the United states is in the northern urban areas and along the gulf and south Atlantic Coasts from Texas to Florida.

Etiology

Smoking

Today, the epidemiology of lung cancer is the epidemiology of smoking. Other factors are relatively of minor importance.

Carcinogens

Cigarette smoke contains a number of proven carcinogens in both the particulate and gaseous phase including:
-Aromatic Hydrocarbons
-Nitrosamines
-Nitrosonormicotine
-Polonium
-Arsenic

Synergic

Exposure to certain substances have a synergic effect in being causatively associated with the use of tobacco products in development of lung cancer.
-Asbestos
-Chloromethyl Ethers
-Mustard Gas
-Radioactive Ore

Host Factors

As with most illnesses, the development of disease depends on a complex interaction between the environment and the host. Specifically with lung cancer, host factors play a relatively minor role.
-Risk of Second Primary
-Associated Malignancies
-CLL
-Aryl Hydrocarbon Hydroxylase
-Scar Carcinoma
-Tuberculosis

Pathology
Bronchogenic carcinomas begin as a small focus of atypical epithelial cells within the bronchial mucosa. As the lesion progresses, the atypia becomes frankly malignant and the neoplasm grows in size. The neoplasm may grow into the bronchial lumen, along the mucosa or into the bronchial wall and adjacent lung parenchyma. Eventually the neoplasm spreads to regional lymph nodes and distant organs such as the liver, brain and bone. Most bronchogenic carcinomas form a mass in or near the hilus. Some neoplasms, especially the adenocarcinomas, form a mass in the periphery of the lung. Refer to Figure 15-42 in your textbook. The following classification scheme represents the major histologic types of bronchogenic carcinoma. Refer to Table 15-10 in your textbook.

• Squamous Cell Carcinoma: The neoplasm is composed of malignant squamous cells which may vary in degree of differentiation from tumor to tumor. A well differentiated squamous cell carcinoma may form keratin and intercellular bridges. . Squamous Cell Cancer: most strongly associated with smoking, can be well, moderately or poorly differentiated. The tumor cells are large, with pink cytoplasm and keratinization, forming keratin pearls. In the poorly differentiated carcinomas, the cells are highly atypical with rare individual cell keratinization   CLINICAL NOTE: This neoplasm is most common in men and is closely related to smoking.

• Adenocarcinoma: Adenocarcinoma is the most common lung cancer which usually arises from peripheral small bronchi and is often associated with a scar. Adenocarcinomas tend to be smaller than other bronchogenic carcinomas and located in the periphery of the lung. The tumor cells form glands and secrete mucin. Mucus stains bright pink with mucicarmine stain and PAS after diastase The neoplasm is composed of malignant glandular epithelium which may vary in degree of differentiation from tumor to tumor. Well differentiated neoplasms may form distinct glands, other neoplasms may vary from forming papillary structures to solid neoplasms without any gland formation. 

• A distinctive type of adenocarcinoma is bronchioloalveolar carcinoma. Bronchioloalveolar carcinoma (BAC) classically spreads in a single layer on top of alveolar septa that serve as scaffolding for the malignant cell growth. In half the tumors the cells are tall, well-differentiated, mucin-producing with basally located nuclei. Nonmucinous BAC is composed of tall columnar cells or cuboidal cells growing along the alveolar walls . Bronchioloalveolar carcinoma: The neoplasm is a distinctive form of adenocarcinoma. The neoplasm arises from the epithelium of the terminal bronchiole or the alveolus. The neoplastic cells are columnar, lining alveoli or form palliary growths which project into the alveolus.  The neoplasm, almost always arising in the periphery, is solitary or forms multiple coalescing nodules. CLINICAL NOTE: This neoplasm is the most common type in women and nonsmokers.

• Small cell carcinoma: Small cell carcinoma, regardless of histologic subtype, lacks a defined architectural pattern. It is composed of sheets of haphazardly arranged small cells with scantly cytoplasm. At low power, the tumor appears blue due to the closely opposed nuclei. There are numerous mitotic figures and foci of necrosis are present   The neoplasm is composed of small cells containing dark blue, round nuclei and sparse cytoplasm. These cells resemble (but are not) lymphocytes and are arranged in clusters.  Electron microscopy reveals that these cells contain neurosecretory granules, indicating their origin from neuroendocrine cells. . CLINICAL NOTE: This neoplasm is strongly related to smoking. It is a very aggressive neoplasm, generally having metastasized at the time of diagnosis.
• Large cell carcinoma: The neoplasm is composed of large, undifferentiated malignant cells.

Pathophysiology

• Bronchogenic carcinoma tends to form an intraluminal mass which may partially or completely obstruct the bronchus. The neoplasm also may compress or invade local structures such as aorta, esophagus, superior vena cava or cervical sympathetic chain.
• Bronchogenic carcinoma may present with a variety clinical manifestations but the major findings are cough, weight loss, chest pain and dyspnea. These neoplasms also have the capacity to secrete hormones or hormone-like substances which have a variety of clinical effects.

Natural History

Pre-Detectable

• Beginning with its biological onset (the development of the first frankly malignant cell) and beginning when the disease may first be shown to exist whether through sputum cytology or chest radiography.
• It has been claimed that by the time a tumor is 10 mm in diameter it has already doubled in size 30 times, contains at least one billion cells, and has completed three-fourths of its anticipated existence.

It is likely that during the majority of a lung tumor's existence it will be undetectable by any currently available diagnostic technique.

Detectable-Asymptomatic

• Presence of the disease is potentially demonstrable, yet continues to be without symptoms. The disease is detectable if:
  • The tumor is radiographically evident (5-10 mm in diameter),
  • or  Sputum is positive for malignant cells.

  The duration of this "presymptomstic-detectable" phase is heavily dependent on the cell type involved and on location of the primary tumor. Sputum cytology can be positive for several years before symptoms occur in a progress from undetectable to unresectable within a few short months. Unfortunately, only about 5% of lung cancer diagnoses are made in this phase. These findings are typically made through incidental X-Ray findings during workup of an unrelated condition of through sputum and X-Ray screening of high-risk patients.

Symptomatic Phase

About 95% of all lung cancer diagnoses are made during the phase when the disease has become symptomatic. Carcinoma discovered at this point in its natural history is almost always well advanced. With very few but significant exceptions, symptomatic lung cancer carries poor prognosis. This is because the vast majority of symptoms in this disease are caused by either locally unresectable or metastatic tumor.

Symptoms Grouping

• Primary Tumor :Endobronchial location of the tumor explains many of the symptoms related to primary tumor. If the primary is peripheral and the lesion is in the lung, often the symptoms related to primary tumor are absent.
  • Cough
  • Dyspnea
  • Hemoptysis
  • Pso-obstructive Pneumonia
  • Increase in Sputum
• Distant Metastasis : Several organs or organ systems clearly emerge as the most common sites of distant metastasis for lung carcinoma. These have great bearing on the clinical manifestations of the disease, and are frequently the cause of the clinical manifestations of the disease, and are frequently the cause of the patient's initial presentation!
  • Brain
  • Liver
  • Bone
  • Skin
  • Adrenals
  • Lymph Node
• Paraneoplastic Syndromes : These are an ever-expanding set of intriguing clinical syndromes involving non-metastatic systemic effects which have been noticed to accompany malignant disease on occasion. Some are associated with a specific cell type; others have no such predilection. Most are felt to be biochemically mediated. Some are just plain mysteries.
  • Endocrine
  • Musculoskeletal/Cutaneous
  • Hematologic
  • Neuromuscular
  • Cardiovascular Miscellaneous
  • Hypertrophic Osteoarthropathy
  • Clubbing
  • Acanthosis Nigricans
  • Thrombophlebitis
  • ACTH
  • ADH
  • Hypercalcemia
• Intrathoracic Spread : When carcinoma of the lung causes symptoms though intrathoracic spread, it tends to do so in only two primary ways:
  • By Contiguity
  • Nodal Metastasis

  Whatever the mode of spread, most of the associated symptoms occur once the disease has reached either the chest wall or the mediastinum. If it was central, mediastinal problems tend to occur. If the tumor was located very inferior, diaphragmatic symptoms may be expected. If it began out in the periphery, chest wall problems are usually noted first.

  Clinical problems that result from extension to the chest wall aren't difficult to understand. Since the parietal pleura is one of the few pain-sensitive structures in the area, this may be the first time the patient experiences pain. Pleural effusion is also a common condition related to this process. If the tumor happened to start near the apex of the lung, a syndrome knows as "Pancoast Tumor" may develop, involving complaints related to damage of CB-T1 roots.

• Non-Specific : The following are non-specific symptoms due to tumor burden:
  • Weight loss
  • Malaise
  • Loss of appetite

Staging

During the past years, numerous investigators have been endeavoring to establish a standard terminology that would accurately describe the extent of a cancer. One such staging system for lung cancer has been formulated by the Task Force on Lung Cancer of the American Joint Committee for Cancer Staging and End-Results Reporting (AJCF). The AJC staging system employs the T-N-M nomenclature . In this system, the letter T represents the primary tumor N regional node involvement, M.

T. Numerical Suffix Assignment

The criteria are:

• Size
• Proximity to Carina
• Extent of Collapse
• Invasion of surrounding structures

N Numerical Suffix Assignment

The first station lymph nodes are the intrapulmonary, peribronchial and hilar lymph nodes, which are contained within the visceral reflections. Second station lymph nodes are those in the mediastinum and may be paraesophageal, subcarinal, paratracheal, aortic or retrotracheal. Involvement of scalene, contra-lateral or extra-thoracic nodes is considered distant metastasis.

 

M Suffix Assignment

The metastatic status is signified by the letter "M" with subscripts O or 1 to indicate absence or presence of metastatic disease. "M1" signifies presence of metastasis in one or more distant organs. The common metastatic sites are Brain, Bone, Liver, Adrenal glands and subcutaneous tissue.

 

Group Staging

T, N and M combinations are used to group stage lung cancer. The staging is important in planning therapy and for estimating prognosis.

Principles of Therapy

Therapeutic options consist of:

Surgery

Non-small cell cancer in stages 1, 2, 3a in acceptable general condition as a surgical candidate are best suited for this modality. In general, small cell cancer is not a surgical disease.

 

Radiation Therapy

If the general condition precludes the patient from being a surgical candidate, Radiation therapy is chosen. Palliative Radiation therapy has an important role for relief of symptoms in inoperable cases.

 

Chemotherapy

Chemotherapy is the treatment of choice for small cell cancer. Its role in NSCC is under investigation.

 

Supportive Care

One needs to consider the following in to determine the best option.

• Cell type
• Stage
• Clinical status

Prevention

Lung cancer is a preventable disease. If cigarette consumption is stopped, we can probably prevent 99% of lung cancers. As a physician, it is your obligation to set an example by not smoking and to advise patients not to smoke. You can offer options to aid patients in quitting their habit.

• Nicotine chewing gum or patches
• Clinics which specialize in helping patients quit smoking
• Hypnotherapy

Take an active role in bringing legislation to curb the use of cigarettes in public places. Additionally, advertisements should be discontinued which encourage children to start the habit. We probably should not attempt to ban cigarettes completely. It is unlikely to succeed, as we have learned from our past experience in trying to ban alcohol.