LUNG CARCINOMA

Lung carcinoma is the most common fatal malignancy in both men and women. In the United
States, it accounts for 14% to 15% of all new cancers and 26% to 30% of all cancer deaths.
Lung cancer is more common in men than women, but at present its incidence is decreasing
in men and increasing in women.

RISK FACTORS FOR LUNG CANCER
Tobacco smoking accounts for 80% to 90% oflung cancers. In smokers, the risk of lung
cancer correlates with younger age at the onset of smoking, the duration and cumulative
amount of exposure, and the depth of inhalation. Heavy smoking is associated with a 20- to
30-fold increase in lung cancer risk compared to nonsmokers. A decrease in risk following
smoking cessation has been demonstrated. Well differentiated squamous cell carcinoma,
small cell carcinoma, large cell carcinoma, and to a lesser extent adenocarcinoma all
demonstrate an increased incidence with increasing cigarette consumption. About 25% of
lung cancers in nonsmokers have been attributed to second-hand smoke. Increasing age is
associated with an increased risk of lung cancer. Lung cancers are rare in patients under age
30. Occupational exposures to various substances have been linked to lung cancer; as many
as 10% of lung cancer cases may be due to occupational exposure. Agents associated with
occupational lung cancer include arsenic, nickel, cluomium, asbestos, beryllium, cadmium,
chromium, mustard gas, pesticides, and radon or uranium. Asbestos exposure is the best-
recognized occupational risk for lung cancer and is the most frequent exposure in the general
population (Fig. 3-1). A dose-response relationship between the severity and duration of
asbestos exposure and the likelihood of developing lung cancer is well established, although
the risk of exposure depends not only on the amount of asbestos to which one is exposed but
also the fiber type (increased risk with amphibole fibers), the industrial use of asbestos, the
conditions of exposure, and the presence of asbestosis. The risk of lung cancer in a heavily
exposed asbestos worker is about five times that of a nonexposed subject Also, smoking is a
synergistic risk in asbestos-exposed subjects: the risk of lung cancer in an asbestos worker
who is a heavy smoker is about 20 times that of a nonsmoking asbestos worker and 100 times
that of a nonexposed nonsmoker (Table 3-1).
Diffuse pulmonary fibrosis has been associated with a 10-fold increase in the risk of lung
cancer. In addition, patients with focal lung scarring. particularly as a result of tuberculosis,
can develop a carcinoma in association with areas of fibrosis or scarring. Although this is
infrequent, cases of carcinoma arising in areas of focal scarring, so-called scar carcinoma, are
encountered in clinical practice. Chronik obstructive lung disease (chronic bronckitis and
emphysema) is a risk factor for developing lung cancer, independent of cigarette smoking. In
both chronic obstructive pulmonary disease (COPD) and diffuse pulmonary fibrosis,
proposed mec:b.anisms of increased cancer risk include decreased clearance of inhaled
carcinogens and epithelial metaplasia.
Genetic: predisposition plays a role in the development of lung cancer. In general, relatives of
subjects with lung cancer have a higher risk of developing lung cancer (about twofold) than
the general population. An increased risk of lung cancer has been associated with specific
oncogenes, chromosome defects, specific HLA antigens, enzyme defects, and defects in
proteins normally produced by tumor suppressor genes.

CELL TYPES OF LUNG CANCER
Lung carcinomas have been classified by the World Health Organization (WHO) based on
their light-microscopic appearances (Table 3-2). The large majority of lung cancers are
classified by WHO criteria as one of four major histologic types: squamous cell carcinoma,
adenocarcinoma, small cell carcinoma, and large cell carcinoma. Numerous subtypes of these
four major twnors have also been defined, but most of these are unimportant from a
radiologic or clinical standpoint. These cell types are not absolutely distinct. As many as 50%
of lung twnors have mixed appearances. and the most differentiated feature of the carcinoma
is used to define its cell type. Many tumors classified as one histologic type (e.g., large cell
carcinoma) using light microscopy and the WHO system would be reclassified if electron
microscopy were used. Cytologic examination uncommonly allows a specific cell type to be
determined; cytologic diagnosis of lung cancer is usually limited to the designation nonsma!l
ceU lung carcinoma (NSCLC) or smaH cell carcinoma.
Preinvasive Lesions
These lesions are dysplastic or localized and include atypical adenomatous hyperplasia
(AAH), squamous dysplasia and carcinoma in situ, and diffuse idiopathic pulmonary
neuroendocrine cell hyperplasia (described below along with carcinoid tumors). AAH
represents a bronchioloalveolar proliferation that resembles but does not meet the criteria for
bronchioloalveolar carcinoma (BAC). Its incidence ranges from 5% to 20%. Most lesions are
5 mm or less in diameter, and lesions are often multiple. AAH is most often found
incidentally in pathologic specimens but may mimic lung carcinoma radiographically
(particularly on cr), leading to resection. On CT, AAH typically appears as a small nodule of
ground-glass opacity.