Benign and malignant neoplasms of various tissue origin that are not specific to the respiratory system can originate in the lung, they usually have the same characteristics as all the others of the same tissue of origin.
The majority of the tumors exclusively found in the respiratory system originate from the bronchial epithelium and are classified in the category of bronchogenic tumors. These neoplasms are most often malignant, very few however are benign, a percentage of the carcinoid tumor formerly classified as bronchial adenoma and the benign lesions of mesenchymal origin are two examples of the benign lesions that can be found in the lung.
This is one of the most common neoplasm of human, representing 22% of all malignancies in the males and 10% of malignancies in the females. This group of neoplasms is still the leading cause of cancer-related death in the USA representing 33% in men and 24% in women. The ratio of male/female incidence that was originally 10 to 1 has narrowed down to less than 3 to 1 due to the increase use of tobacco by the female population, tobacco being one of the major etiological factor in the development of most pulmonary neoplasms.
The peak incidence is between the ages of 40 and 70 years.
Etiology
Several factors are implicated in the etiology of the tumors:
Cigarette smoking: There is a definite link between tobacco smoking and lung tumors based on several observations:
First the statistical evidence showing a 10-fold greater risk in smokers, with a higher risk in heavy smokers and a reduced risk in people who stop smoking for at least 10 years.
The clinical evidence of atypical changes in the epithelial lining of the bronchial tree in about 97% of smokers versus 0.9% of non smokers.
Experimental evidence of multiple carcinogenic substances in cigarette smoke.
Industrial hazards:
Radiation exposure of all types
Inhalation of Uranium
Exposure to Asbestos, with a higher risk of cancer when there is associated cigarette smoking.
Prolonged contact with other substances like nickel, chromate, mustard gas arsenic, beryllium and iron has also beem implicated as factors inn the etiology of carcinoma of the lung.
Air pollution, this includes indoor and outdoor exposure.
Molecular Genetics : Any of the previously cited factors may cause some genetic mutations that in the long run lead to neoplastic changes in the human lung cells through DNA damage.
Scar tissue : The scar tissue has to be present before the onset of the tumor not to be confused with the desmoplasia that occurs in response to certain neoplasm
Pathogenesis
The pathogenesis of bronchogenic carcinoma is the same regardless of the etiology. The lesion usually starts with some alterations in the bronchi consisting in: loss of ciliae, hyperplasia, metaplasia and dysplasia of the lining epithelium. Most tumors of the lung originate from the epithelial lining of the large bronchi, very often near the hilus, few arise from the small bronchi or from the alveolar lining.
Evolution of the tumor
The neoplasm usually starts as a small area of atypical epithelial alteration that progresses to an elevated ulcerated mass. The progress of the neoplastic growth varies, the initial lesion may continue to grow inside the lumen of the bronchus like a projecting mass, it may infiltrate the wall of the bronchus and even invade the peribronchial tissue including the mediastinum and the pericardium. Some of the malignancies may diffusely invade the lung tissue.
In all the different patterns of growth, the tumors are bulky, grey-white in color and firm in consistency, and if large enough may show areas of necrosis and hemorrhage. In advanced cases, when the tumor has invaded a large portion of the lung, the initial lesion is often found inside a large bronchus as a projecting papillary or fungating mass. Metastases occur very early in the course of the disease, the hilar, the paratracheal, the mediastinal and the scalene lymph nodes are the first to be affected. Distant metastasis through hematogenous or lymphatic spread may occur even before the primary lesion is discovered, and about 50% of the metastases occur first in the adrenal glands. The average five-year survival rate depends on several factors including the histological variety, the staging and the grading of the tumor.
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Histological Varieties of Bronchogenic
Carcinoma
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| Non small cell carcinoma | |
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25 to 40% |
Adenocarcinoma |
25 to 40% |
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| Undifferentiated small cell carcionoma | 20 to 25% |
Oat cell (lymphocyte-like) |
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Intermediate (polygonal) |
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| Large cell carcinoma | 10 to 15% |
| Pleomorphic carcinoma | |
Undifferentiated |
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The staging of the tumor is the most important prognostic factor in the evaluation of the patient.
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International Staging System
for Bronchogenic Carcinoma
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Stage Grouping
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| Stage I a |
T 1
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N 0
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M 0
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| Stage I b |
T 2
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N 0
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M 0
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| Stage II a |
T 1
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N 1
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M 0
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| Stage II b |
T 2 T 3 |
N 1 N 0 |
M 0 M 0 |
| Stage III a |
T 1-3 T 3 |
N 2 N 1 |
M 0 M 0 |
| Stage III b |
Any T T 3 T 4 |
N 3 N 2 Any N |
M 0 M 0 M 0 |
| Stage IV |
Any T
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Any N
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M 1
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The New International Staging
System for Lung Cancer
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T Values
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T 1
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Tumor <= 3 cm without pleural or mainstream bronchus involvement |
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T 2
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Tumor > 3 cm or involvement of mainstream bronchus >= 2 cm from carina, visceral, pleural, or lobar atelectasis. |
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T 3
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Tumor with involvement of chest wall (including superior sulcus tumors), diaphragm, mediastinum, mainstream bronchus < 1 cm from carina or entire lung atelectasis |
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T 4
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Tumor with invasion of mediastinum, heart, great vessels, trachea, esophagus, vertebral body, or carina or with a malignant pleural effusion |
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The New International Staging
System for Lung Cancer
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N Values
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N 0
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No demonstrable metastasis toregional lymph nodes |
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N 1
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Ipsalateral hilar or peribronchial nodal involvement |
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N 2
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Metastasis to ipsilateral mediastinal or subcarinal lympn nodes |
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N 3
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Metastasis to contralateral mediastinal or hilar lymph nodes |
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The New International Staging
System for Lung Cancer
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M Values
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M 0
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No (known) distant metastasis |
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M 1
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Distant metastasis present |
Several factors have to be considered in the study of Bronchogenic carcinoma:
The location
The frequency of occurrence between male/female
The prognosis
NON SMALL CELL LUNG CARCINOMA
SQUAMOUS CELL CARCINOMA
Squamous cell carcinoma of the lung, the second most common variant after Adenocarcinoma, originates usually from the metaplastic lining epithelium of the large bronchi, most often at the hilus. This type of bronchogenic carcinoma is closely related to cigarette smoking and is more common among men. It has a faster local growth pattern than the other types but metastases appear much later.
The squamous cell carcinoma of the lung is usually well differentiated and shows all the characteristic histology features like pearl formation and intercellular bridges. However less differentiated forms of the tumor can be seen, and are often classified as "Undifferentiated large cell tumor" or "Pleomorphic tumor" of the lung.
ADENOCARCINOMA
BRONCHIAL ADENOCARCINOMA - SOLID , ACINAR, PAPILLARY TYPE
This variety of bronchogenic carcinoma representing one third of all lung cancers arises from the lining epithelium of the small bronchi, the relationship of this variety of bronchogenic carcinoma to cigarette smoking is less obvious and less direct than with the other varieties (squamous cell and small cell carcinoma), the incidence of adenocarcinoma of the lung in smokers is only three times that of non smokers. This could be due to the formation of scar tissue which seems to be the common finding in smokers and non-smokers who develop this variety of lung tumor. It is not prevalent among males, in the younger age-group(<40) it is seen more often in women
This tumor is usually located at the periphery of the lungs where scar tissue can be seen and shows a slower local growth pattern than the squamous type.
Iin latest studies, it was demonstrated that the post therapy survival rate of patients with adenocarcinoma of the lung was not influenced by the age, the gender of the patient or by history of cigarette smoking or not.
On microscopy, there are mucin producing cells arranged in a glandular or a pseudo-glandular pattern in a solid stroma (solid type), Well developed acini can be identified (acinar type), Some papillary structures may be seen (papillary tumor). All variants invade and replace the normal lung tissue.
Certain varieties of this tumor, like the squamous cell variant, may be poorly differentiated and classified as Pleomorphic or Undifferentiated Large cell .
BRONCHIOLO- ALVEOLAR CARCINOMA
This variety of lung tumors arises from the terminal Broncho alveolar units, originating most probably from the stem cells of the terminal bronchioles. These cells are basically capable of differentiate into any of the normal cellular components of the distal units, namely: the Bronchoalveolar cells, type ll alveolar cells or the non ciliated columnar cells of the terminal bronchioles (Clara cells). These tumors are equally distributed among men and women and may occur at any age. This variety of lung tumor shows the same etiologic factors as the bronchial adenocarcinoma. About 45% of these tumors metastasize and the overall survival rate is 25% after 5 years.
On gross examination, one or several nodules of various sizes are located mostly at the periphery of the lung. The nodules are firm in consistency and have a gray translucent cut surface. This is the only variety of bronchogenic carcinoma that does not completely destroy the architecture of the lung.
On microscopic examination, the tumor is composed of alveolar-like structures lined by cuboidal and mucin producing columnar cells showing variable degree of anaplasia. There are large papillae protruding inside spaces containing desquamated tumor cells and multinucleated giant cells.
UNDIFFERENTIATED SMALL CELL CARCINOMA OF THE LUNG
This very aggressive lung tumor seems to have a direct and strong correlation with cigarette smoking and is characterized by early metastasis. It originates from the enterochromaffin (Kulchitsky) cells present in the neonatal bronchial epithelium and is commonly associated with the production of ectopic hormone (paraneoplastic syndrome). Because of the presence of neurosecretory granules responsible for the secretion of the various polypeptide hormones, this tumor has been classified as a neuroendocrine lesion of the APUD (Amine precursor uptake decarboxylation) type, that may at time cause the carcinoid syndrome through serotonin secretion.
PATHOLOGY
On gross examination, the small cell tumor is often located at the hilus or at the center of the lung.
On microscopy, this tumor is composed of small epithelial cells with very little cytoplasm. The cells may be oval, round or spindled in shape.
The small oval type is known as the oat cell carcinoma of the lung
The elongated or intermediate type as spindled or polygonal small cell carcinoma.
There is a small percentage of the undifferentiated tumors that are of mixed cell type, namely small cell/large cell mixture. These tumors have a poorer prognosis than the pure small cell tumor. One observation has been made regarding this tumor: chemotherapy seems to induce transformation of the pure small cell type to a mixed cell type which worsens the prognosis and affects the overall survival of the patients.
The prognosis of the undifferentiated small cell carcinoma as a whole is poor, the worst of all lung tumors, even with treatment, the mean survival is one year from the time of diagnosis. Only 3% of the cases are alive after 5 years.
PLEOMORPHIC CARCINOMA or UNDIFFERENTIATED LARGE CELL TUMOR
This category of neoplasms of the lung includes all the different types of lung tumors that do not show enough specific characteristics to be classified in any of the previously described groups. The cell pattern may be mixed or pure but the dominant features are the spindle cells. The break down is as follow:
Pure spindle 9.4%
Mixed 90%
The mixed pattern include:
Squamous/spindle
Adeno/spindle
Giant cell/spindle
The pure form of spindle tumor may be difficult to differentiate from the desmoplasia of an undifferentiated carcinoma.
These neoplastic lesions are usually very aggressive and show marked degree of anaplasia.
The cells are large, irregular in shape and have vesiculated nuclei, some variety may contain intranuclear mucin, others may be spindled with a sarcomatous appearance.
A feature common to a large group of these tumors is the presence of multinucleated giant cells scattered throughout the lesion, which warrants the name of "giant cell tumors" given to these neoplasms.
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IMPORTANCE OF STAGING IN MANAGEMENT OF LUNG CANCER The staging of lung cancer has an important bearing on prognosis. In addition once tumors are past a certain stage they are regarded as inoperable. Careful staging is a pre-requisite to surgical intervention in lung cancer. The key elements that offer a reasonable prospect of success with surgery are: Tumor must be within a lobar bronchus or at least 2 cm distal to the carina.
No direct extension to chest wall, diaphragm pericardium No involvement of heart, great vessels, trachea, esophagus or vertebrae. No malignant pleural effusion No contralateral nodal involvement No distant metastases MISCELLANEOUS TUMORS OF THE LUNGS In this category are included all the different malignant lesions of the lung that are not specific to the lung tissue, these tumors may arise from any of the basic components and take the characteristics of the tissue of origin. |
Kaposi Sarcoma
One tumor of mesenchymal origin has lately been increasing in frequency, the Kaposi sarcoma, found in the lungs of a great majority of patients who died of AIDS. This is a form of vascular lesion (hemangiosarcoma) with an extensive involvement of the supporting stroma.
This tumor consists of multiple small nodules scattered throughout the lung tissue, they resemble granulomata and consist of proliferated spindle cells, incompletely formed vascular structures, extravasated blood components and hemosiderin-laden macrophages. The endothelial lining of the vessels shows some degree of anaplastic activity and the stromal cells are very active. There are also slit-like spaces not lined with endothelium and filled with blood cells.
Pulmonary Blastoma
This rare tumor of the respiratory system arises from a multipotential cell of the embryo. It may appear at any age as a well demarcated white solid mass.
On microscopic examination it is made of tube-like cords of epithelial cells, irregular glands supported by an immature stroma of spindled and stellate cells.
Some a these tumors may send metastasis.
Few cases of Adenoid Cystic Carcinoma " ACC of the lung have been reported. These tumors have the same characteristics as the ACC that occur in the salivary glands, but they seem to be more aggressive than the salivary gland tumors with the same histological pattern, since they may send widespread metastases.
The ACC usually show three patterns of growth, cribriform, tubular and solid. The cells are small with dark compact nuclei arranged in the same pattern as in the salivary gland tumor. Local recurrence is common after surgical removal of the tumor.
METASTATIC TUMORS TO THE LUNGS
These are the most common malignancies found in the lungs, the invasion of the lungs is done via the lymphatics, the blood or by contiguity. The lesions are usually multiple and more numerous at the periphery of the lungs, around the blood vessels and the lymphatics. They show the typical "cannon ball" appearance on X-Ray, feature that allows for the differentiation with the satellite lesion of a primary tumor. The lesions usually show the characteristics of the primary tumor on histological examination.
BENIGN TUMORS OF THE LUNGS
BRONCHIAL CARCINOID
This neoplasm, representing 5% of primary lung tumors, like the small cell carcinoma of the lung arises from the basal layer of respiratory epithelium, the Kulchitsky cells, but unlike the small cell tumor, it bears no relationship to cigarette smoking or other environmental factors. It occurs mostly in the young, usually before the age of 40 year, with equal frequency in the male or the female.
This tumor once believed to be a bronchial adenoma is now proven more aggressive, since local invasion and distant metastasis have been reported in certain cases. Two variants of the tumor are described:
Atypical Carcinoid
The aggressive cases representing about 10% of all bronchial carcinoid are known as "Atypical carcinoid", they carry a poor prognosis with a recurrence rate of 50% after 2 years and a survival rate of less than 50% after 5 years. Regional lymphnodes metastases are found in about 40% and liver metastases in about 5 to 15% of these cases.
Typical Carcinoid
The remaining 90% of the cases are the non aggressive Typical carcinoid that carry a good prognosis, with a survival rate of 90 to 95% after 5 years.
The distinction between the two variants relies on the histopathologic findings. The number of mitoses is less than 5 in a 10 power field in the typical carcinoid, versus 7 to 10 in the atypical carcinoid at the same magnification.
The carcinoid tumor of the lungs is often associated with the carcinoid syndrome showing the cardinal symptoms resulting from neuroendocrine secretion predominantly serotonin. The other symptoms pertinent to the location of the tumor include: hemoptysis, bronchiectasis, emphysema and atelectasis of the pulmonary tissue.
PATHOLOGY
On gross examination, the carcinoid tumor consists of small polypoid projections inside a large bronchus (Central carcinoid tumor), rarely, however a bronchial carcinoid may originate at the periphery of the lung (Peripheral carcinoid tumor).
On microscopy, there are groups and cords of small cells separated by thin septa of connective tissue. The cells are regular in shape with uniform nuclei showing rare mitoses. The neurosecretory granules can be demonstrated by electron microscope study. The more aggressive lesions may show some degree of pleomorphism.
HAMARTOMA OF THE LUNG.
This benign tumor of the lung is usually discovered as an incidental opaque lesion in a routine Xray. It is small (3-4cm), mostly solid, and is composed mostly of cartilage, fibrous tissue, fat, blood vessels and rare cystic spaces lined with respiratory epithelium. Some of these lesions are made of cores of fibrous tissue lined by single layer of cuboidal epithelium, these tumors are usually referred to as adenofibromas.
PARANEOPLASTIC SYNDROME OF LUNG TUMORS
About 3 to 10% of bronchogenic tumors are associated with various systemic symptoms forming what is known as the paraneoplastic syndrome. These symptoms are the result of secretion of certain hormones or hormone-like substances by the tumors, and can appear before the lesion becomes clinically evident.
The hormones and hormone-like substances more often identified are: ACTH, ADH, Serotonin and Parathormones. Any of these substances can be secreted by any of the different histology variety of bronchogenic tumors. But, certain hormones are more characteristic of certain type of tumors. For example:
ACTH secretion leading to Cushing syndrome and ADH secretion that cause severe hyponatremia are characteristic of the small cell carcinoma of the lung.
Serotonin secretion leading to carcinoid syndrome is often the result of a small cell carcinoma and more so the result of a bronchial carcinoid tumor.
Secretion of Parathormones resulting in hypercalcemia is more characteristic of squamous cell carcinoma of the lung.
Hematologic and Cardiovascular symptoms like DIC, Thrombophlebitis, Bacterial endocarditis are most often complications of an Adenocarcinoma of the lung.
The location of the bronchogenic carcinoma which is usually a space occupying lesion may have some local effects on the surrounding lung tissue and on the surrounding organs. This includes:
The Pancoast syndrome consisting of:
Peripheral neuropathy characterized by shoulder and arm pain along the distribution of the eight cervical nerve and the first and second thoracic nerve.
Muscle weakness and atrophy forming what is known as Eaton – Lambert syndrome. This is due to secretion of autoimmune antibodies that affect the neuronal calcium channel.
Horner's syndrome characterized by ptosis of the eyelids, enophtalmos, myosis and anhidrosis on the same side as the lesion.
Peripheral neuropathy mainly sensory in nature
Dermatologic manifestations
Hematologic abnormalities (leukemoid reaction).
The Secondary Pathology Syndrome
In this syndrome, the location of the tumor inside the lung causes some local alterations in the surrounding lung tissue. These include:
- Emphysema due to the partial obstruction of the bronchi by a tumor mass
- Atelectasis due to total obstruction of a bronchus
- Bronchitis, Bronchiectasis and Lung abscesses due to impaired drainage of the bronchi
- Congestion and Edema due to intrapulmonary vascular compression.
On the surrounding organs, the changes that usually occur include:
The superior vena cava syndrome, the result of compression or invasion of the vena cava by the tumor, venous congestion edema and circulatory anomalies
Pleuritis and Pleural effusion, result of invasion of the pleura by the tumor.
Pericarditis may result from the extension of the tumor to the pericardium
Most pathologic lesions of the pleura are secondary complications of another underlying disease. The two types of lesions that commonly affect the pleura are:
The inflammatory diseases and
The neoplastic growths.
Regardless of the etiology, pleural lesions are often associated with certain degree of pleural effusion.
INFLAMMATORY DISEASES OF THE PLEURA
The inflammatory reaction of the pleura also known as pleuritis is in most cases associated with pleural effusion. The physical characteristic of the effusion is not always the same, it varies with the etiology of the disease, and also provides a base for a classification. The common varieties of pleural effusions include:
SEROFIBRINOUS PLEURAL EFFUSION.
This variety of effusion is an exudate and is the result of acute inflammatory reaction of the pleura. When present in the pleural cavity, this type of exudate is the result of a reaction of the pleura to an intrapulmonary lesion like tuberculosis, pneumonia, infarct, abscess or bronchiectasis. On occasion, a fibrinous pleural effusion may be the reaction of the pleura to a systemic disease like it occurs in Rheumatoid arthritis, Systemic Lupus Erythematosus and Uremia.
It is important to differentiate the pleural effusion caused by an inflammatory lesion (exudate) from the pleural effusion due to the transudation of fluid as a result of a circulatory disturbance (transudate).
The characteristics of the exudate of a pleuritis are usually uniform and are as follow:
Exudate
Straw colored
Contains multiple epithelial, mesothelial, inflammatory cells
Has a specific gravity ranging from 1,016 to 1,020.
Is most often unilateral
In most cases leave sequel through organization of the precipitate.
Transudate (hydrothorax) has the following characteristics:
It is clear, watery
It contains very few cells mainly lymphocytes
It has a specific gravity of about 1,012
It is usually bilateral
It usually resorbs without permanent damage to the pleura and the underlying lung tissue.
SUPPURATIVE OR PURULENT PLEURAL EFFUSION
This is usually due to a bacterial or mycotic infection of the pleura. This effusion is characteristically yellow-green in color and is made of purulent material. When the purulent material diffusely covers the pleura, it is referred to as Pyothorax" when the pus is sealed into pockets delineated by fibrous tissue it is referred to as Empyema. This type of exudate may lead to tough fibrous adhesions between the pleural surfaces (parietal and visceral), and in case of tuberculous pleuritis, to calcification of the pleura.
HEMORRHAGIC PLEURAL EFFUSION
Hemorrhagic exudate in the pleural cavity is most often due to neoplastic lesions of the lung and the pleura, may result from some form of Rickettsial disease or can be a sign of pulmonary asbestosis.
HEMOTHORAX
The presence of pure blood in the pleural cavity also known as Hemothorax is often due to the rupture of an aortic aneurysm. Hemothorax is fatal in most cases, rarely however the escape of blood in the pleural space may be small enough to be controlled.
HYDROTHORAX
Hydrothorax consists of accumulation of transudate fluid in the pleural cavity. It occurs as a result of hemodynamic changes in the general circulation like an increase in the hydrostatic pressure . Accumulation of transudate fluid in the pleural cavity is not due to inflammatory reaction of the pleura. The most common causes are congestive heart failure, pulmonary edema and congestion, or any fluid extravasation resulting from systemic cause like the decrease of oncotic pressure in nephrotic syndrome or an increase in the intrapleural negative pressure. Hydrothorax is usually bilateral and ordinarily resorbs without permanent alteration of the pleura.
CHYLOTHORAX
Accumulation of chyle in the pleural cavity is usually the result of occlusion of the major lymphatic ducts by a tumoral mass . It is more commonly seen in the left side, but at time can be bilateral. The fluid has a milky appearance and contains emulsified fat.
PNEUMOTHORAX
This refers to the presence of air or gas in the pleural cavities.
The spontaneous form usually found in the young may be idiopathic or may be due the rupture of a peripheral bleb, rarely a spontaneous pneumothorax may be the sign of an underlying pulmonary disease like asthma, emphysema, tuberculosis, pulmonary abscess or a peripheral cyst.
The traumatic form of pneumothorax is caused by a penetrating wound of the chest wall that may or may not enter the lung tissue.
The therapeutic form of pneumothorax, no longer in use, consisted in the introduction of air inside the pleural space to create a positive pressure and collapse of the lung leading to obliteration of cavitary lesions (ex: secondary TB).
ASBESTOS RELATED PLEURAL LESIONS
Asbestos exposure may lead to various pleural lesions, the most common being pleural effusion, diffuse pleural fibrosis, pleural plaques and pleural mesothelioma.
The pleural effusions associated with asbestosis are usually serous in nature, or at time hemorrhagic.
The diffuse fibrous thickening of the pleura may obliterate the pleural cavity by creating adhesions between the parietal and the visceral pleura.
Pleural plaques the most common sign of asbestos exposure, are localized dense areas of fibrosis more pronounced on the anterior and posterolateral areas of the parietal pleura and over the diaphragmatic dome. The plaques are made of collagenous bands showing extensive areas of calcification. Asbestos bodies are not usually found in the pleural plaques, however, following digestion of the tissue, some asbestos fibers can be seen with electron microscopic examination.
Pleural mesothelioma will be described later.
TUMORS OF THE PLEURA
Metastatic tumors are more commonly found in the pleura than the primary tumors, the source of the metastasis being the lungs and the breasts in most cases. Rarely however, a remote tumor may metastasize to the pleura, the ovaries being the most common source of metastasis from distant organ. The metastatic tumors to the pleura cause a sero-sanguinous type of pleural effusion containing multiple malignant cells showing the characteristics of the primary lesion.
PRIMARY MALIGNANT TUMORS OF THE PLEURA
PLEURAL MESOTHELIOMA
Two different types of pleural mesothelioma have been described:
A BENIGN or LOCALIZED MESOTHELIOMA which is not a complication of asbestos exposure. This tumor is located most often on the pleural surface to which it may be attached by a thin pedicle, it is firm to the touch, varies in size, and does not cause pleural effusion. On microscopy it is composed of spindled cells supported by a fibrous stroma, feature that makes the differential diagnosis with a fibroma very difficult.
A MALIGNANT or DIFFUSE MESOTHELIOMA. About 50% of the cases admit or recall any exposure to asbestos, since the main etiological factor to this tumor is exposure to asbestos fibers and about 20% of the cases will have other concurrent signs of asbestosis. The risk of developing the mesothelioma does not seem to increase with the concomitant use of tobacco as it occurs with bronchogenic carcinoma. This tumor of the pleura may appear 20 to 45 years after the initial exposure to asbestos, and about 2 to 3% of people exposed to asbestos develop this pleural lesion and 7 to 10% in heavily exposed patients. The pathogenesis of the pleural mesothelioma in relation to the exposure to asbestos is not very clear, the only constant feature is the close contact of the asbestos fibers with the pleura either in workers with direct contact with the fibers or relatives of the workers or in people living in proximity of an asbestos factory. The fibers are transported to the pleura through lymphatic drainage.
Pathology
Examination reveals a thick layer of pink gelatinous tissue covering large areas of the pleural surface, the interlobar septa and encasing the lung and at time, other thoracic structures. Malignant mesothelioma is often associated with hemorrhagic pleural effusion.
Microscopic examination reveals two different patterns of the tumor:
A sarcomatoid pattern showing elongated spindled cells resembling a fibrosarcoma.
An epithelial pattern made of papillary structures lined with cuboidal or columnar cells that may mimic an adenocarcinoma.
A mixed pattern may show elements of both.
The definite diagnosis of the mesothelioma is done by histochemical and electron microscopy studies that include detection of acid mucopolysaccharide, identification of long microvilli and the presence of keratin protein; the mesothelioma is however negative for neutral mucin stain and carcinoembryonic antigen (CEA).
The prognosis is generally hopeless, very few patients survive more than two years after the initial symptoms.
File updated August 21, 2001
© M. Kavanagh, M.D.