USMF



Respiratory system Chronic disorders

CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

Lung tumors

Introduction

Obstructive pulmonary disease

Restrictive pulmonary disease

Lung tumors

introduction

• Obstructive pulmonary disease

o diseases that cause increased resistance to airflow due to obstruction at any level

o asthma, chronic bronchitis, emphysema, bronchiectasis

• Restrictive pulmonary disease

o diseases caused by reduced expansion of lung

▪ chest wall disorders, such as idiopathic adolescent scolliosis

▪ girls affected 8 times more than boys

o acute or chronic interstitial and infiltrative diseases, i.e., ARDS or pneumoconioses

COPD refers to the diseases of asthma, chronic bronchitis, emphysema, bronchiectasis. All of these diseases affect the terminal airways of the lung. They are all characterized clinically by a chronic or recurrent obstructive pattern on pulmonary function testing-- hence the term obstructive lung disease. COPD affects 15 million Americans and costs an estimated 18 billion dollars anually. Death rate in men is 2 times higher than in women,; however, the death rate of COPD in man appears to be flat since the 1970's, while in women, especially African-american women, the death rate has increased.

Objectives

1. Recall that COPD is strongly correlated with air pollution and smoking.

2. Recognize changes associated with chronic bronchitis and emphysema.

3. Compare and contrast pathologic changes in centrilobular (centriacinar) and panacinar (panlobular) emphysema.

4. Recognize the most common risk factors for lung cancer.

5. List the histologic types of lung cancer.

6. Briefly describe the pathogenesis and prognosis of lung cancer.

7. Discuss the growth patterns and clinical symptoms of carcinoid tumors.

8. Discuss the growth patterns of metastatic tumors.

9. Describe the histologic features of pulmonary hamartomas.

Key words: emphysema, acini, bronchoectasias. Small cell (Oat Cell) carcinoma

Adenocarcinoma, Bronchioloalveolar carcinoma, Large cell carcinoma, Squamous cell carcinoma, Pancoast's or Superior Sulcus Tumor, Paraneoplastic Syndromes,

Ectopic Hormone Secretion.

clinical objectives:

1. Describe the gross and microscopic appearance of lung tissue in emphysema.

2. Describe the gross and microscopic appearance of lung tissue in chronic bronchitis.

3. Describe the gross and microscopic appearance of lung tissue in bronchial asthma.

4. Recognize the microscopic pattern of lung in bronchoectasias.

5. Recognize the gross and microscopic appearance of lung cancer.

Pathology of Chronic Obstructive Pulmonary Disease:

Chronic Bronchitis and Emphysema

Although chronic bronchitis and emphysema frequently occur together, each may be seen clinically and pathologically as separate entities. The incidence and severity of COPD are strongly correlated with air pollution and smoking. Although the mortality from lung cancer exceeds that of COPD, the earlier onset and prolonged morbidity of COPD lends it a greater socioeconomic impact. Both chronic bronchitis and emphysema are more common in men than in women.

Chronic Bronchitis

This condition is defined by clinical parameters, specifically the presence of a persistent cough productive of sputum for at least 3 months, in at least 2 consecutive years. Chronic bronchitis, so common among habitual smokers and inhabitants of smog-laden cities, is not nearly as trivial as was once thought. When persistent for years, it may (1) progress to chronic obstructive airway disease, (2) lead to cor pulmonale and heart failure, or (3) cause atypical metaplasia and dysplasia of the respiratory epithelium, providing a rich soil for cancerous transformation. Important definitions in bronchitis include the following:

Involvement and Pathologic Changes

The pathologic changes of chronic bronchitis are found in the bronchi and/or bronchioles. In some cases, involvement of both small and large airways is present, whereas in others, one may predominate or be absent.

Large airway (bronchial) involvement is clinically manifest as cough and sputum production. The histologic changes consist of :

• increased numbers of goblet cells in the epithelium

• increased volume of the submucosal mucus glands

The latter is judged by determining the Reid index, which is defined as the ratio of the width of the submucosal gland mass to the distance from the basal lamina of the mucosa to the inner perichondrium. A ratio greater than 0.4 indicates mucus gland enlargement.

In addition to the increase in mucus-secreting cells and glands, there is usually a component of chronic inflammation in the airway wall, but the amount of this infiltrate may be highly variable.

The histology of small airway (bronchiolar) involvement consists of the presence of goblet cells in the lining epithelium. Goblet cells are normally rare or absent in the distal airways. Involvement of bronchioles may be manifest as a decrease in maximum forced expiratory flow, since mucus in the lumen of the small airways can produce an increased resistance to flow. As in the large airways, there may also be a component of inflammation.

Superimposed acute inflammation in the airways of a patient with chronic bronchitis may contribute to exacerbation of symptomatology due to increased cellular infiltrates and edema.

ASTHMA

Asthma is a chronic inflammatory disorder of the airways that causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night and/or in the early morning. These symptoms are usually associated with widespread but variable bronchoconstriction and airflow limitation that is at least partly reversible, either spontaneously or with treatment. It is thought that inflammation causes an increase in airway responsiveness (bronchospasm) to a variety of stimuli. Some of these stimuli would have little or no effect on nonasthmatics with normal airways. Many cells play a role in the inflammatory response, in particular eosinophils, mast cells, macrophages, T lymphocytes, neutrophils, and epithelial cells.

Morphology. The morphologic changes in asthma have been described principally in patients dying of status asthmaticus, but it appears that the pathology in nonfatal cases is similar. Grossly, the lungs are overdistended because of overinflation, and there may be small areas of atelectasis.

This cast of the bronchial tree is formed of inspissated mucus and was coughed up by a patient during an asthmatic attack.

The most striking macroscopic finding is occlusion of bronchi and bronchioles by thick, tenacious mucous plugs. Histologically, the mucous plugs contain whorls of shed epithelium, which give rise to the well-known Curschmann spirals. Numerous eosinophils and Charcot-Leyden crystals are present; the latter are collections of crystalloid made up of eosinophil membrane protein. The other characteristic histologic findings of asthma, collectively called "airway remodeling" (Fig. 15-12), include:

• Thickening of the basement membrane of the bronchial epithelium

• Edema and an inflammatory infiltrate in the bronchial walls, with a prominence of eosinophils and mast cells

• An increase in size of the submucosal glands

• Hypertrophy of the bronchial wall muscle

Between the bronchial cartilage at the right and the bronchial lumen filled with mucus at the left is a submucosa widened by smooth muscle hypertrophy, edema, and inflammation (mainly eosinophils). These are changes of bronchial asthma. The peripheral eosinophil count or the sputum eosinophils can be increased during an asthmatic attack.

The classic asthmatic attack lasts up to several hours and is followed by prolonged coughing; the raising of copious mucous secretions provides considerable relief of the respiratory difficulty. In some patients, these symptoms persist at a low level all the time. In its most severe form, status asthmaticus, the severe acute paroxysm persists for days and even weeks, and under these circumstances, ventilatory function might be so impaired as to cause severe cyanosis and even death. The clinical diagnosis is aided by the demonstration of an elevated eosinophil count in the peripheral blood and the finding of eosinophils, Curschmann spirals, and Charcot-Leyden crystals in the sputum. In the usual case, with intervals of freedom from respiratory difficulty, the disease is more discouraging and disabling than lethal. With appropriate therapy to relieve the attacks, patients with asthma are able to maintain a productive life. Occasionally, the disease disappears spontaneously.

While airflow obstruction is primarily attributed to muscular bronchoconstriction, the airway remodeling may contribute as well.

Emphysema

Emphysema is defined by morphologic parameters, i.e. abnormal permanent enlargement of airspaces distal to the terminal bronchiole, accompanied by the destruction of their walls. The component of wall destruction distinguishes emphysema from simple over-inflation.

Emphysema occurs in different forms, based on the anatomic distribution of the process.

The pulmonary acinus comprises those components of the lung distal to a terminal bronchiole, i.e., respiratory bronchioles, alveolar ducts, alveolar sacs and alveoli. The acinus is not exactly the same as the pulmonary lobule, but for practical purposes, these two terms are often interchanged, hence the terminology that follows for the different types of emphysema.

Centrilobular (centriacinar) emphysema

Consists of dilatation of the central structures of the acinus (respiratory bronchioles and alveolar ducts). Early in the disease, the peripheral portions of the acinus are spared.

Grossly, this form of emphysema typically affects the upper lobes earlier and more severely than the lower lobes. Patients are typically cigarette smokers. Cut surface of the lung parenchyma typically shows foci of dilated spaces surrounded by relatively normal tissue.

Diagram of normal structures within the acinus, the fundamental unit of the lung. A terminal bronchiole (not shown) is immediately proximal to the respiratory bronchiole. B, Centriacinar emphysema with dilation that initially affects the respiratory bronchioles. C, Panacinar emphysema with initial distention of the peripheral structures (i.e., the alveolus and alveolar duct); the disease later extends to affect the respiratory bronchioles.

Microscopically, the distribution of the lesions may be difficult to discern. The destruction of alveolar septal walls is evident by the presence of septa unattached to adjacent alveoli. Fibrosis is not a feature of diffuse centrilobular emphysema.

Late in the course of the disease, the destruction of septa and dilatation of airspaces may extend to involve all portions of the acinus, creating an appearance that resembles panacinar emphysema. Usually, however, one can still find areas of the lung where there is the patchy dilatation typical of centrilobular emphysema.

Panacinar (panlobular) emphysema

Affects all portions of the acini (respiratory bronchioles, alveolar ducts and sacs, alveoli). This form of emphysema is associated with alpha-1 antitrypsin deficiency, and typically affects the lower lobes earliest and most severely.

Grossly, cut surface of the lung shows diffuse enlargement of airspaces in the affected parenchyma. Often the enlarged spaces are traversed by delicate, spider-web-like strands representing the residual alveolar walls. As in centrilobular emphysema, fibrosis is not seen.

In any of the forms of emphysema, dilated airspaces my enlarge to a size greater than 2 cm in dimension. An enlarged space of this size may be referred to as a "bulla." The term "bullous emphysema" does not connote a specific type of emphysema. Bullae may be clinically important because of their tendency to rupture, resulting in pneumothorax.

In centrilobular and panacinar emphysema, the clinical symptoms of obstructive lung disease result from the increased resistance to expiratory flow that occurs as small airways, no longer supported by the elastic recoil of alveolar septa, collapse during expiration.

The chest cavity is opened at autopsy to reveal numerous large bullae apparent on the surface of the lungs in a patient dying with emphysema. Bullae are large dilated airspaces that bulge out from beneath the pleura. Emphysema is characterized by a loss of lung parenchyma by destruction of alveoli so that there is permanent dilation of airspaces.

On cut section of the lung, the dilated airspaces with emphysema are seen. Although there tends to be some scarring with time because of superimposed infections, the emphysematous process is one of loss of lung parenchyma, not fibrosis.

Microscopically at high magnification, the loss of alveolar walls with emphysema is demonstrated. Remaining airspaces are dilated.

Pathogenesis

The destruction of portions of the alveolar septal walls has been related to an imbalance of protease-antiprotease activity in the lung. Patients with alpha-1 antitrypsin deficiency have a relative increase in protease activity. Cigarette smokers tend to have more neutrophilis and macrophages recruited to the alveolar parenchyma, compared with non-smokers. These two cell types are the major source of proteases and elastases in the lung.

In patients with severe emphysema, cough is often slight, overdistention is severe, diffusion capacity is low, and blood gas values are relatively normal at rest. Such patients may overventilate and remain well oxygenated and therefore are somewhat ingloriously designated as pink puffers (see Table 15-4). Patients with chronic bronchitis more often have a history of recurrent infection, abundant purulent sputum, hypercapnia, and severe hypoxemia, prompting the equally inglorious designation of blue bloaters. Development of cor pulmonale and eventual congestive heart failure, related to secondary pulmonary vascular hypertension, is associated with a poor prognosis. Death in most patients with COPD is due to (1) respiratory acidosis and coma, (2) right-sided heart failure, and (3) massive collapse of the lungs secondary to pneumothorax. Treatment options include bronchodilators, steroids, bullectomy, and, in selected patients, lung volume reduction surgery and lung transplantation.

Bronchiectasis

It is defined as a chronic necrotizing infection within airways that leads to permanent dilatation and scarring of airway walls.

Bronchiectasis is a disease characterized by permanent dilation of bronchi and bronchioles caused by destruction of the muscle and elastic tissue, resulting from or associated with chronic necrotizing infections. To be considered bronchiectasis, the dilation should be permanent; reversible bronchial dilation often accompanies viral and bacterial pneumonia. Because of better control of lung infections, bronchiectasis is now an uncommon condition. It is manifested clinically by cough, fever, and expectoration of copious amounts of foul-smelling, purulent sputum. Bronchiectasis develops in association with a variety of conditions, which include the following

• Congenital or hereditary conditions, including cystic fibrosis, intralobar sequestration of the lung (discussed earlier in this chapter), immunodeficiency states, and primary ciliary dyskinesia and Kartagener syndromes (discussed later)

• Postinfectious conditions, including necrotizing pneumonia caused by bacteria (Mycobacterium tuberculosis, Staphylococcus aureus, Haemophilus influenzae, Pseudomonas), viruses (adenovirus, influenza virus, HIV), and fungi (Aspergillus species)

• Bronchial obstruction, owing to tumor, foreign bodies, and occasionally mucus impaction, in which the bronchiectasis is localized to the obstructed lung segment

• Other conditions, including rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, and post-transplantation (chronic lung rejection, and chronic graft-versus-host disease after bone marrow transplantation)

An excellent example that illustrates the pathogenesis of bronchiectasis is the inherited disorder known as cystic fibrosis. Recurrent or persistent mucous plugging in this disorder of mucous production results in obstruction followed by air resorption beyond the level of blockage. The distal lung collapses and cannot be properly cleaned by the normal lung mechanisms. Infection develops in the blocked segments with resultant necrosis and permanent damage to the airway walls. Over time the airways dilate as their walls become weakened.

Other hereditary conditions are associated with bronchiectasis.

Localized bronchiectasis may occur after severe infection. The damaged area often becomes a focus for recurrent lung infection and may have to be surgically removed.

Patients with bronchiectasis have low grade fever, cough, shortness of breath and foul smelling (sometimes bloody) sputum. They frequently "flare" into full blown pneumonia.

Morphology. Bronchiectasis usually affects the lower lobes bilaterally, particularly air passages that are vertical, and is most severe in the more distal bronchi and bronchioles. When tumors or aspiration of foreign bodies leads to bronchiectasis, the involvement may be sharply localized to a single segment of the lung.

Once the dilated bronchi are present, as seen here grossly in the mid lower portion of the lung, the patient has recurrent infections because of the stasis in these airways. Copius purulent sputum production with cough is typical.

The airways are dilated, sometimes up to four times normal size. These dilations may produce long, tubelike enlargements (cylindrical bronchiectasis) or, in other cases, may cause fusiform or even sharply saccular distention (saccular bronchiectasis).

Characteristically, the bronchi and bronchioles are sufficiently dilated that they can be followed, on gross examination, directly out to the pleural surfaces. By contrast, in the normal lung, the bronchioles cannot be followed by ordinary gross dissection beyond a point 2 to 3 cm removed from the pleural surfaces. On the cut surface of the lung, the transected dilated bronchi appear as cysts filled with mucopurulent secretions.

The histologic findings vary with the activity and chronicity of the disease. In the full-blown, active case, there is an intense acute and chronic inflammatory exudation within the walls of the bronchi and bronchioles, associated with desquamation of the lining epithelium and extensive areas of necrotizing ulceration. There may be pseudostratification of the columnar cells or squamous metaplasia of the remaining epithelium. In some instances, the necrosis completely destroys the bronchial or bronchiolar walls and forms a lung abscess. Fibrosis of the bronchial and bronchiolar walls and peribronchiolar fibrosis develop in the more chronic cases, leading to varying degrees of subtotal or total obliteration of bronchiolar lumina.

In the usual case of bronchiectasis, a mixed flora can be cultured from the involved bronchi, including staphylococci, streptococci, pneumococci, enteric organisms, anaerobic and microaerophilic bacteria, and (particularly in children) Haemophilus influenzae and Pseudomonas aeruginosa. In ABPA, a few fungal hypae can be seen on special stains within the muco-inflammatory contents of the cylindrically dilated segmental bronchi. In late stages, the fungus may infiltrate the bronchial wall.

Clinical Course. Bronchiectasis causes severe, persistent cough; expectoration of foul-smelling, sometimes bloody sputum; dyspnea and orthopnea in severe cases; and occasional life-threatening hemoptysis. A systemic febrile reaction may occur when powerful pathogens are present. These symptoms are often episodic and are precipitated by upper respiratory tract infections or the introduction of new pathogenic agents. In the full-blown case, the cough is paroxysmal in nature. Such paroxysms are particularly frequent when the patient rises in the morning, and changes in position lead to drainage into the bronchi of the collected pools of pus. Obstructive ventilatory insufficiency can lead to marked dyspnea and cyanosis. Cor pulmonale, metastatic brain abscesses, and amyloidosis are less frequent complications of bronchiectasis.

Lung Carcinomas

Lung cancer is currently the most frequently diagnosed major cancer in the world and the most common cause of cancer mortality worldwide. This is largely due to the carcinogenic effects of cigarette smoke. Over the coming decades, changes in smoking habits will greatly influence lung cancer incidence and mortality as well as the prevalence of various histologic types of lung cancer.

Risk Factors

Tobacco Smoke Several lines of evidence strongly link tobacco use with the development of lung cancer:

• The majority (at least 80%) of lung cancers occur in cigarette smokers.

• The risk of developing lung cancer is 10-20 times greater in male cigarette smokers than in non-smokers.

• There is a direct correlation between the incidence of lung cancer and the prevalence of cigarette smoking in men and women.

• The risk of developing lung cancer correlates with the number of cigarettes smoked and the duration of the habit.

• Cessation of smoking reduces the risk of developing lung cancer.

• Smokers have a much higher incidence of atypical cytologic changes in bronchial epithelium than do non-smokers. (The relationship of these changes to the development of neoplasia is debated).

• Cigarette smoke contains carcinogenic substances.

Since not all cigarette smokers develop lung cancer, other factors, such as genetic predisposition, may play a role in the development of neoplasia. Lung carcinoma also occurs in non-smokers, but is much less common in this population. 

Occupational Exposure Lung carcinoma is linked to exposure to certain dusts and metals, for example, nickel, chromates, arsenic, beryllium, and asbestos.

Radiation The incidence of lung cancer increased in survivors of the atomic bomb blasts in Japan. Uranium miners have an increased risk of lung cancer compared with non-miners. Exposure to radon has been linked to lung cancer.

Fibrosis/Scarring in the Lung Peripheral lung cancers are sometimes associated with areas of fibrous scar. In most cases of these "scar cancers," the fibrosis may result from, rather than precede the development of the neoplasia. Some lung cancers arise in the setting of diffuse interstitial fibrosis.

Histologic Types

Squamous Cell Carcinoma

• strong association with cigarette smoking

• histologically defined by keratinization or intercellular bridging

• majority occur centrally (i.e., associated with a bronchus)

• may attain large size

• may cavitate

• may be associated with hypercalcemia

The pink cytoplasm with distinct cell borders and intercellular bridges characteristic for a squamous cell carcinoma are seen here at high magnification.

In this squamous cell carcinoma at the upper left is a squamous eddy with a keratin pearl. At the right, the tumor is less differentiated and several dark mitotic figures are seen.

Adenocarcinoma

• most common histologic type in non-smokers and women

• histologically defined by glandular differentiation or mucin production

• majority occur in periphery of lung

• peripheral tumors sometimes associated with fibrous "scar"

• may be difficult to distinguish from metastatic carcinoma

Subtype: Bronchioloalveolar Carcinoma

• tumor cells grow along pre-existing alveolar septa

• may present as a solitary mass, multiple nodules, or a diffuse process

• well-differentiated, diffuse form may be associated with abundant mucus production

Small cell carcinoma

• strong association with cigarette smoking

• "undifferentiated" tumor composed of small cells (i.e., high nuclear/cytoplasmic ratio, very little cytoplasm; sometimes referred to as "oat cell")

• most cases arise centrally

• high incidence of extrapulmonary spread at diagnosis

• histologic type most commonly associated with ectopic hormone production

• represents the most malignant end of the spectrum of neuroendocrine tumors of the lung

Large Cell Carcinoma

• includes any non-small cell carcinoma that does not display obvious squamous or glandular differentiation

• "giant cell" subtype has very poor prognosis

•

Growth Patterns and Clinical Manifestations

Intrapulmonary Growth

• Tumor growing in a bronchus may cause bronchial irritation and mucosal erosion leading to cough and/or hemoptysis.

• Obstruction of a bronchus may result in post-obstructive pneumonia, abscess formation, atelectasis, or air trapping.

• Peripheral (subpleural) tumors may be clinically silent and detected incidentally on chest x-ray.

Extrapulmonary Intrathoracic Growth

• Centrally located tumors may invade the mediastinum.

• Compression and/or invasion of the superior vena cava causes superior vena cava syndrome, (i.e., dusky cyanosis with distension of veins of the head, neck, and upper extremities)

• Invasion of the recurrent laryngeal nerve may lead to hoarseness.

• Peripherally located tumors may invade the pleura, causing pain.

• Apically-located tumors (Pancoast's or Superior Sulcus Tumor) may invade the brachial plexus, causing arm pain, and/or the cervical sympathetic plexus, causing Horner's syndrome, (i.e., ipsilateral enophthalmos, ptosis, meiosis and anhidrosis).

Metastatic Growth

• Regional metastasis occurs to bronchopulmonary and mediastinal lymph nodes.

• Distant metastasis frequently occurs to extrathoracic lymph nodes, liver, bone, brain, and adrenal glands

• Symptoms related to metastatic disease may be the first manifestation of a lung carcinoma.

Paraneoplastic Syndromes

Some tumors are associated with symptoms not attributable to their growth pattern, such as:

• Lambert-Eaton syndrome--symptoms resembling myasthenia gravis

• hypertrophic pulmonary osteoarthropathy--with periostitis, clubbing of digits, and sometimes arthritis

• myopathy

Ectopic Hormone Secretion

Some lung cancers are associated with symptoms related to secretion of hormonal substances (e.g., ACTH, ADH, calcitonin, gonadotropins). Small cell carcinomas are more frequently associated with this activity than other histologic types, although hypercalcemia due to parathromone activity is most often associated with squamous cell carcinoma.

Pathogenesis

Most lung carcinomas probably arise from an undifferentiated basal or stem cell in the bronchial epithelium that has undergone malignant transformation. These cells normally have the potential to differentiate into surface cells, mucus cells, or neuroendocrine cells in the bronchial mucosa. Carcinomas often display differentiation along one or more of these cell lines.

Recent work has demonstrated the presence of mutational changes in certain oncogenes in lung carcinomas. Carcinogenesis in the lung, as in other sites, probably involves activation of oncogenes and/or loss of tumor suppressor genes.

Prognosis

Prognosis in lung carcinoma depends on the clinical staging at the time of diagnosis, and to some extent on the histologic type.

Overall prognosis for lung carcinoma is poor, with five year survival rates of only 10-15%. This is because approximately 65% of patients with lung cancer present with Stage III disease. Patients with Stage I disease (small, localized, resectable tumor) may have 50% or better five-year survival rates.

Small cell carcinoma is associated with the worst prognosis of all the major histologic types because of the high frequency of metastatic spread at initial diagnosis. Squamous cell carcinomas tend to grow more slowly than other histologic types. In general, poorly differentiated tumors of any histologic type behave more aggressively than better differentiated tumors.

Carcinoid Tumors

Statistics

These neuroendocrine tumors comprise 1-5% of all lung tumors. The male:female incidence ratio is roughly equal. Most patients are under age 40, but this tumor may be seen in older individuals as well.

Risk Factors No risk factors have been identified. There is no known relationship to cigarette smoking.

Histologic Features

These tumors have neuroendocrine features, with uniform cells arranged in organoid, ribbon or rosette patterns. Mitotic activity is low, and necrosis is absent. These tumors are usually very vascular. Ultrastructurally, tumor cells contain dense-core granules typical of neuroendocrine neoplasias. The tumor cells may be demonstrated to contain one or several peptides by immunohistochemistry.

Growth Patterns and Clinical Symptoms

Central (Bronchial)

Carcinoid tumor typically grows as a polypoid mass projecting into the lumen of a bronchus. Usually the tumor also infiltrates into the peribronchial tissue. Because of the intralumenal growth, this tumor often produces cough and/or post-obstructive pneumonia, atelectasis or air trapping.

Peripheral

Some carcinoid tumors arise in peripheral lung parenchyma, associated with a small bronchiole. Because of the peripheral location, the tumor is usually clinically silent and only found incidentally on chest x-ray.

Secretory activity

A small percentage of pulmonary carcinoid tumors produce the classic carcinoid syndrome (diarrhea, flushing, cyanosis). Most do not.

Metastatic Growth

Most pulmonary carcinoid tumors do not metastasize; however, some of these tumors spread to regional lymph nodes, and a small percentage metastasize distantly, usually to the liver.

Pathogenesis

These tumors probably arise from stem cells that differentiate along the line of Kultschitzsky cells, the normal cells of the bronchial mucosa that have neuroendocrine properties. Similar tumors arise in the gastrointestinal tract.

Prognosis

Carcinoid tumors are low-grade malignant neoplasms. The majority of these tumors are slow-growing and do not metastasize. Five year survival rate is approximately 90%.

Metastatic Tumors in the Lung

The lung is one of the most common locations to which carcinomas of other viscera will metastasize; thus, metastatic tumor in the lung occurs more frequently than primary carcinoma of the lung.

Growth Patterns and Clinical Presentation

Multiple Nodules

The most common pattern of growth is that of multiple tumor nodules involving multiple lobes. Clinical symptoms may be absent or may be related to involvement of airways.

Solitary nodule

Occasionally, metastatic tumor may occur as a single mass in the lung. In these cases, clinical distinction from a primary lung cancer may be difficult. The tumor may involve a bronchus or the peirpheral parenchyma. Clinical symptoms will depend on the location. Primary sites from which solitary metastases not infrequently occur include kidney, colon and thyroid.

Lymphangitic spread

Rarely, metastatic tumor may diffusely infiltrate the pulmonary lymphatics, giving rise to an appearance of an interstitial pattern on chest x-ray, with or without a nodular pattern. The clinical symptoms also may mimic those of an interstitial disease process.

Histologic Features

The histology of metastatic carcinoma resembles that of the primary tumor. Since adenocarcinoma is the most common histologic type of primary cancer arising in the viscera, it is the most common histology found in metastatic cancer in the lung. There may be marked similarity to primary adenocarcinoma of the lung; thus, clinical history and knowledge of the x-ray appearance are important in interpretation.

There is a high incidence of pulmonary metastasis from sarcomas of soft tissue and bone. Metastatic sarcoma usually presents as multiple nodules.

Benign Neoplasms of the Lung

Benign tumors of the lung are relatively rare, compared to carcinoma of the lung. The most common of the benign tumors is the hamartoma. 

The term "hamartoma" refers to a tumor composed of a mixture of mature tissue types that are normally present in the organ in which it arises. Pulmonary hamartomas are usually composed of a mixture of cartilage, fibrous tissue and fat. The tumor usually presents as a solitary nodule on chest x-ray. Often it is present in the periphery of the lung, and is clinically silent. Less often, it may involve a bronchus. These tumors are usually surgically resected because of a clinical concern of carcinoma. Excision is curative.

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