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د.سرى سلمان عجام
RESPIRATORY DISEASES
Lung Tumors
Avariety of benign and malignant tumors may arise in the lung, but 90%
to 95% are carcinomas, about 5% are bronchial carcinoids, and 2% to 5%
are mesenchymal and other miscellaneous neoplasms
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
Etiology and Pathogenesis
1-Tobacco Smoking.-
2-Industrial Hazards.
High-dose ionizing radiation
Asbestos exposure
3-Air Pollution.
Radon is a ubiquitous radioactive gas that has been linked
epidemiologically to increased lung cancer
4-Molecular Genetics.
5-Precursor Lesions.
(1) squamous dysplasia and carcinoma in situ,
(2) atypical adenomatous hyperplasia
(3) diffuse idiopathic pulmonary neuroendocrine cell hyperplasia
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Histologic(WHO) Classification of Malignant Epithelial Lung
Tumors
Squamous cell carcinoma
Small-cell carcinoma
Combined small-cell carcinoma
Adenocarcinoma
Acinar; papillary, bronchioloalveolar, solid, mixed subtypes
Large-cell carcinoma Large-cell neuroendocrine carcinoma
Adenosquamous carcinoma
Carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements
Carcinoid tumor
Typical, atypical
Carcinomas of salivary gland type
Unclassified carcinoma
Metastasis of carcinoma
Extension may occur to the pleural surface and then within the pleural
cavity or into the pericardium. Spread to the tracheal, bronchial, and
mediastinal nodes can be found in most cases. The frequency of nodal
involvement varies slightly with the histologic pattern but averages
greater than 50%.
Distant spread of lung carcinoma occurs through both lymphatic and
hematogenous pathways. These tumors often spread early throughout the
body except for squamous cell carcinoma,
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Squamous Cell Carcinoma.
Squamous cell carcinoma is most commonly found in men and is
closely correlated with a smoking history.
they tend to arise centrally
in major bronchi and spread to local hilar nodes but they disseminate
outside the thorax later than the other types.
Large lesions undergo necrosis and cavitation
Histologically, this tumor is characterized by the presence of
keratinization and/or intercellular bridges. Keratinization may take the
form of squamous pearls or individual cells with markedly eosinophilic
dense cytoplasm . These features are prominent in the well-differentiated
tumors, are easily seen but not extensive in moderately differentiated
tumors, and are focally seen in poorly differentiated tumors. Mitotic
activity is higher in poorly differentiated tumors. In the past, most
squamous cell carcinomas were seen to arise centrally from the segmental
or subsegmental bronchi. However, the incidence of squamous cell
carcinoma of the peripheral lung is increasing. Squamous metaplasia,
epithelial dysplasia, and foci of frank carcinoma in situ may be seen in
bronchial epithelium adjacent to the tumor mass
Adenocarcinoma.
This is a malignant epithelial tumor with glandular differentiation or
mucin production by the tumor cells. Adenocarcinomas grow in various
patterns, including acinar, papillary, bronchioloalveolar, and solid with
mucin formation.
Adenocarcinoma is the most common type of lung
cancer in women and nonsmokers
As compared with squamous cell cancers, the lesions are usually more
peripherally located, and tend to be smaller. They vary histologically
from well-differentiated tumors with obvious glandular elements to
papillary lesions resembling other papillary carcinomas to solid masses
with only occasional mucin-producing glands and cells.
Adenocarcinomas grow more slowly than squamous cell carcinomas but
tend to metastasize widely and earlier
Bronchiolo alveolar carcinoma arises from terminal bronchioloalveolar
region It grows on preexisting structure (alveolar wall) without its
destruction there is no evidence of stromal, vascular, or pleural invasion
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it is proposed that adenocarcinoma of the lung arises from atypical
adenomatous hyperplasia progressing to bronchioloalveolar carcinoma,
which then transforms into invasive adenocarcinoma but not all
adenocarcinomas arise in this manner, nor do all bronchioloalveolar
carcinomas become invasive if left untreated.
Small Cell Carcinoma.
have a strong relationship to cigarette smoking; only about 1% occur in
nonsmokers. They may arise in major bronchi or in the periphery of the
lung. There is no known preinvasive phase or carcinoma in situ. They are
the most aggressive of lung tumors, metastasize widely, and are virtually
incurable by surgical means
The occurrence of neurosecretory granules, the ability of some of these
tumors to secrete polypeptide hormones suggest derivation of this tumor
from neuroendocrine progenitor cells of the lining bronchial epithelium.
This lung cancer type is most commonly associated with ectopic hormone
production
Microscopic features
This highly malignant tumor has a distinctive cell type.
The epithelial cells are relatively small, with scant cytoplasm, ill-defined
cell borders, finely granular nuclear chromatin (salt and pepper pattern),
and absent or inconspicuous nucleoli.
The cells are round, oval, or spindle-shaped,
nuclear molding is prominent.
There is no absolute size for the tumor cells, but in general they are
smaller than three small resting lymphocytes.
The mitotic count is high.
The cells grow in clusters that exhibit neither glandular nor squamous
organization. Necrosis is common and often extensive.
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Large Cell Carcinoma.
This is an undifferentiated malignant epithelial tumor that lacks the
cytologic features of small-cell carcinoma and glandular or squamous
differentiation. The cells typically have large nuclei, prominent nucleoli,
and a moderate amount of cytoplasm. Large cell carcinomas probably
represent squamous cell carcinomas and adenocarcinomas that are so
undifferentiated that they can no longer be recognized by light
microscopy
Combined Carcinoma. Approximately 10% of all lung carcinomas have
a combined histology, including two or more of the above types.
Clinical Course.
Lung cancer is one of the most insidious and aggressive neoplasms in the
realm of oncology. In the usual case it is discovered in patients in their
50s whose symptoms are of several months' duration. The major
presenting complaints are cough (75%), weight loss (40%), chest pain
(40%), and dyspnea (20%). Some of the more common local
manifestations of lung cancer and their pathologic bases . Not
infrequently the tumor is discovered by its secondary spread during the
course of investigation of an apparent primary neoplasm elsewhere.
Paraneoplastic Syndromes.
Lung carcinoma can be associated with several paraneoplastic
syndromes, some of which may antedate the development of a
detectablepulmonary lesion. The hormones or hormone-like factors
elaborated include:
• Antidiuretic hormone (ADH), inducing hyponatremia due to
inappropriate ADH secretion
• Adrenocorticotropic hormone (ACTH), producing Cushing
syndrome
• Parathormone,
parathyroid
hormone-related
peptide,
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prostaglandin E, and some cytokines, all implicated in the
hypercalcemia often seen with lung cancer
• Calcitonin, causing hypocalcemia
• Gonadotropins, causing gynecomastia
• Serotonin and bradykinin, associated with the carcinoid syndrome
The incidence of clinically significant syndromes related to these factors
ranges from 1% to 10% of all lung cancer patients, although a much
higher proportion of patients show elevated serum levels of these (and
other) peptide hormones. Any one of the histologic types of tumors may
occasionally produce any one of the hormones, but tumors that produce
ACTH and ADH are predominantly small cell carcinomas, whereas
those that produce hypercalcemia are mostly squamous cell tumors..