Tumors of The Lung

A variety 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.[60]
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.[138]
The number of new cases of lung cancer occurring in 2008 in the United States is estimated to be 215,020
(note that in 1950 it was 18,000), accounting for about 15% of cancer diagnoses and 29% of cancer-related
deaths. The annual number of deaths from lung cancer in the United States is estimated to be 161,840 in
2008.[139] Since the early 1990s lung cancer incidence and mortality rates have been decreasing in men, most
likely from the decreased smoking rates over the past 30 years. However, decreases in smoking patterns
among women lag behind those of men. Since 1987 more women have died each year of lung cancer than of
breast cancer, which for over 40 years had been the major cause of cancer death in women. Cancer of the
lung occurs most often between ages 40 and 70 years, with a peak incidence in the 50s or 60s. Only 2% of
all cases appear before the age of 40. The outlook for individuals diagnosed with lung cancer is dismal. The
1-year survival rate has increased from 34% in 1975 to 41% in 2007, largely because of improvements in
surgical techniques. However, the 5-year rate for all stages combined is only 16%.
Etiology and Pathogenesis.
Most carcinomas of the lung, similar to cancer at other sites, arise by a stepwise accumulation of genetic
abnormalities that transform benign bronchial epithelium to neoplastic tissue. Unlike many other cancers,
however, the major environmental insult that inflicts genetic damage is known. We begin our discussion with
the well-known lung carcinogencigarette smoke.
Tobacco Smoking.
The evidence provided by statistical and clinical observations establishing a positive relationship between
tobacco smoking and lung cancer is overwhelming. Experimental data have also been pursued, but this
approach is limited by species differences.
Statistical evidence is most compelling: 87% of lung carcinomas occur in active smokers or those who
stopped recently. In numerous retrospective studies, there was an invariable statistical association between
the frequency of lung cancer and (1) the amount of daily smoking, (2) the tendency to inhale, and (3) the
duration of the smoking habit. Compared with nonsmokers, average smokers of cigarettes have a tenfold
greater risk of developing lung cancer, and heavy smokers (more than 40 cigarettes per day for several
years) have a 60-fold greater risk. Women have a higher susceptibility to tobacco carcinogens than men do.
Cessation of smoking for 10 years reduces risk but never to control levels. It should be noted, however, that
despite compelling evidence supporting the role of cigarette smoking, only 11% of heavy smokers develop
lung cancer in their lifetime. Clearly, there are other (genetic) factors involved as will be discussed later.
Epidemiologic studies also show an association between cigarette smoking and carcinoma of the mouth,
pharynx, larynx, esophagus, pancreas, uterine cervix, kidney, and urinary bladder. Secondhand smoke, or
environmental tobacco smoke, contains numerous human carcinogens for which there is no safe level of
exposure. It is estimated that each year about 3000 nonsmoking adults die of lung cancer as a result of
breathing secondhand smoke.[140] Cigar and pipe smoking also increase risk, although much more modestly
than smoking cigarettes. The use of smokeless tobacco is not a safe substitute for smoking cigarettes or
cigars, as these products cause oral cancers and can lead to nicotine addiction.
Clinical evidence is obtained largely through observations of histologic changes in the lining epithelium of the
respiratory tract in habitual smokers. These sequential changes have been best documented for squamous
cell carcinoma, but they may also be present in other histologic subtypes. In essence, there is a linear
correlation between the intensity of exposure to cigarette smoke and the appearance of ever more worrisome
epithelial changes that begin with squamous metaplasia and progress to squamous dysplasia, carcinoma in

situ, and invasive carcinoma. Lung tumors of smokers frequently contain a typical, though not specific,
molecular fingerprint in the form of G : C > T : A mutations in the p53 gene that are probably caused by
benzo[a]pyrene, one of the many carcinogens in tobacco smoke.[138]
Experimental work has consisted mainly of attempts to induce cancer in experimental animals with extracts
of tobacco smoke.[141] More than 1200 substances have been counted in cigarette smoke, many of which are
potential carcinogens. They include both initiators (polycyclic aromatic hydrocarbons such as
benzo[a]pyrene) and promoters, such as phenol derivatives. Radioactive elements may also be found
(polonium-210, carbon-14, and potassium-40) as well as other contaminants, such as arsenic, nickel, molds,
and additives. Protracted exposure of mice to these additives induces skin tumors. Efforts to produce lung
cancer by exposing animals to tobacco smoke, however, have been unsuccessful. The few cancers that have
developed have been bronchioloalveolar carcinomas, a type of tumor that is not strongly associated with
smoking in humans.
Industrial Hazards.
Certain industrial exposures increase the risk of developing lung cancer. High-dose ionizing radiation is
carcinogenic. There was an increased incidence of lung cancer among survivors of the Hiroshima and
Nagasaki atomic bomb blasts. Uranium is weakly radioactive, but lung cancer rates among nonsmoking
uranium miners are four times higher than those in the general population, and among smoking miners they
are about 10 times higher.
The risk of lung cancer is increased with asbestos. Lung cancer is the most frequent malignancy in individuals
exposed to asbestos, particularly when coupled with smoking.[80] Asbestos workers who do not smoke have a
five times greater risk of developing lung cancer than do nonsmoking control subjects, and those who smoke
have a 50 to 90 times greater risk. The latent period before the development of lung cancer is 10 to 30
years.
Air Pollution.
Atmospheric pollutants may play some role in the increased incidence of lung carcinoma today. Attention has
been drawn to the potential problem of indoor air pollution, especially by radon.[142,][143] Radon is a ubiquitous
radioactive gas that has been linked epidemiologically to increased lung cancer in miners exposed to
relatively high concentrations. The pathogenic mechanism is believed to be inhalation and bronchial
deposition of radioactive decay products that become attached to environmental aerosols. These data have
generated concern that low-level indoor exposure (e.g., in homes in areas of high radon in soil) could also
lead to increased incidence of lung tumors; some attribute the bulk of lung cancers in nonsmokers to this
insidious carcinogen ( Chapter 9 ).[144]
Molecular Genetics.
Ultimately, the exposures cited previously are thought to act by causing genetic alterations in lung cells,
which accumulate and eventually lead to the neoplastic phenotype. It has been estimated that 10 to 20
genetic mutations have occurred by the time the tumor is clinically apparent.[145]
As will be discussed below, for all practical purposes lung cancers can be divided into two clinical subgroups:
small cell carcinoma and non-small cell carcinoma. Some molecular lesions are common to both types,
whereas others are relatively specific. The dominant oncogenes that are frequently involved in lung cancer
include c-MYC, KRAS, EGFR, c-MET, and c-KIT. The commonly deleted or inactivated tumor suppressor genes
include p53, RB1, p16(INK4a), and multiple loci on chromosome 3p. At this locale there are numerous
candidate tumor suppressor genes, such as FHIT, RASSF1A, and others that remain to be identified. Of the
various cancer associated genes, C-KIT (4070%), MYCN and MYCL (2030%), p53 (90%), 3p (100%), RB
(90%), and BCL2 (7590%) are most commonly involved in small cell lung carcinoma. By comparison, EGFR
(25%), KRAS (1015%), p53 (50%), p16 INK4a (70%) are the ones most commonly affected in non-small
cell lung carcinoma. In addition recent studies show that LKB1, PTEN, and TSC, all relating to the m-TOR
pathway are also mutated in up to 30% of lung cancers (mostly non-small cell lung carcinoma). [146] It should
be noted that C-KIT is over expressed but only rarely mutated. Hence, drugs that target its tyrosine kinase
domain (such as imatinib) are ineffective. Recall that in tumors with mutation of that kinase domain (e.g.,

gastrointestinal stromal tumor) this drug is useful for treatment. Telomerase activity is increased in over
80% of lung tumor tissues.
There are several signal transduction molecules that are activated in lung cancer, such as AKT,
phosphatidylinositol-3-kinase, ERK1/2, STAT5, and focal adhesion proteins such as paxillin. Although certain
genetic changes are known to be early (inactivation of chromosome 3p suppressor genes) or late (activation
of KRAS), the temporal sequence is not yet well defined. More importantly, certain genetic changes such as
loss of chromosome 3p material can be found in benign bronchial epithelium of individuals with lung cancer,
as well as in the respiratory epithelium of smokers without lung cancers, suggesting that large areas of the
respiratory mucosa are mutagenized after exposure to carcinogens (field effect). [147] On this fertile soil, the
cells that accumulate additional mutations ultimately develop into cancer.
Occasional familial clustering has suggested a genetic predisposition, as has the variable risk even among
heavy smokers. Attempts at defining markers of genetic susceptibility are ongoing and have, for example,
identified a role for polymorphisms in the cytochrome P-450 gene CYP1A1 ( Chapter 7 ).[148] People with
certain alleles of CYP1A1 have an increased capacity to metabolize procarcinogens derived from cigarette
smoke and, conceivably, incur the greatest risk of developing lung cancer. Similarly, individuals whose
peripheral blood lymphocytes undergo chromosomal breakages following exposure to tobacco-related
carcinogens (mutagen sensitivity genotype) have a greater than tenfold risk of developing lung cancer
compared with controls. In addition, large scale linkage studies point to an autosomal susceptibility locus on
6q23-25. More recently, genome-wide association studies have revealed an intriguing link to polymorphisms
in the nicotine acetylcholine receptor gene located on chromosome 15q25 and lung cancer in both smokers
and nonsmokers.[149]
It should also be pointed out that 25% of lung cancers worldwide arise in nonsmokers and these are
pathogenetically distinct. They occur more commonly in women, and most are adenocarcinomas. They tend
to have EGFR mutations, almost never have KRAS mutations and p53 mutations, although common, occur
less commonly. The nature of the p53 mutations are also distinct.[150]
Precursor Lesions.
Three types of precursor epithelial lesions are recognized: (1) squamous dysplasia and carcinoma in situ, (2)
atypical adenomatous hyperplasia, and (3) diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. It
should be noted that the term precursor does not imply that progression to cancer will occur in all cases.
Currently it is not possible to distinguish between precursor lesions that progress and those that remain
localized or regress.
Classification.
Tumor classification is important for consistency in patient treatment and because it provides a basis for
epidemiologic and biologic studies. The most recent classification of the World Health Organization [138] has
gained wide acceptance ( Table 15-10 ). Several histologic variants of each type of lung cancer are
described; however, their clinical significance is still undetermined, except as mentioned below. The relative
proportions of the major categories are[151]:

Adenocarcinoma (males 37%, females 47%)

Squamous cell carcinoma (males 32%, females 25%)

Small cell carcinoma (males 14%, females 18%)

Large cell carcinoma (males 18%, females 10%)

TABLE 15-10 -- Histologic 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
The incidence of adenocarcinoma has increased significantly in the last two decades; it is now the most
common form of lung cancer in women and, in many studies, men as well. [152] The basis for this change is
unclear. A possible factor is the increase in women smokers, but this only highlights our lack of knowledge
about why women tend to develop more adenocarcinomas. One interesting postulate is that changes in
cigarette type (filter tips, lower tar and nicotine) have caused smokers to inhale more deeply and thereby
expose more peripheral airways and cells (with a predilection to adenocarcinoma) to carcinogens. [153] There
may be mixtures of histologic patterns, even in the same cancer. Thus, combined types of squamous cell
carcinoma and adenocarcinoma or of small-cell and squamous cell carcinoma occur in about 10% of patients.
For common clinical use, however, the various histologic types of lung cancer can be clustered into two
groups on the basis of likelihood of metastases and response to available therapies: small cell carcinomas
(almost always metastatic, high initial response to chemotherapy) versus non-small cell carcinomas (less
often metastatic, less responsive). The strongest relationship to smoking is with squamous cell and small cell
carcinoma.
Staging.
A uniform TNM system for staging cancer according to its anatomic extent at the time of diagnosis is
extremely useful, chiefly for comparing treatment results from different centers ( Table 15-11 ).
TABLE 15-11 -- International Staging System for Lung Cancer
T1

Tumor <3 cm without pleural or main stem bronchus involvement (T1a, <2 cm; T1b, 23 cm)

T2

Tumor 37 cm or involvement of main stem bronchus 2 cm from carina, visceral pleural involvement,
or lobar atelectasis (T2a, 35 cm; T2b, 57 cm)

T3

Tumor >7 cm or one with involvement of chest wall (including superior sulcus tumors), diaphragm,
mediastinal pleura, pericardium, main stem bronchus 2 cm from carina, or entire lung atelectasis, or
separate tumor nodule(s) in the same lobe

T4

Tumor with invasion of mediastinum, heart, great vessels, trachea, esophagus, vertebral body, or
carina or separate tumor nodules in a different ipsilateral lobe

N0

No demonstrable metastasis to regional lymph nodes

N1

Ipsilateral hilar or peribronchial nodal involvement

N2

Metastasis to ipsilateral mediastinal or subcarinal lymph nodes

N3

Metastasis to contralateral mediastinal or hilar lymph nodes, ipsilateral or contralateral scalene, or

supraclavicular lymph nodes

M0 No distant metastasis
M1 Distant metastasis (M1a, separate tumor nodule in contralateral lobe or pleural nodules or malignant
pleural effusion; M1b, distant metastasis)

STAGE GROUPING
Stage Ia

T1

N0

M0

Stage Ib

T2

N0

M0

Stage IIa

T1

N1

M0

Stage IIb

T2

N1

M0

T3

N0

M0

T13

N2

M0

T3

N1

M0

Any T

N3

M0

T3

N2

M0

T4

Any N

M0

Any T

Any N

M1

Stage IIIa

Stage IIIb

Stage IV

Adapted from Goldstraw P, et al: The IASLC lung cancer staging project: proposals for the revision of the
TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumors. J
Thorac Oncol 2:706, 2007.
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 are listed in Table 15-12 .
Not infrequently the tumor is discovered by its secondary spread during the course of investigation of an
apparent primary neoplasm elsewhere. Bronchioloalveolar carcinomas, by definition, are noninvasive tumors
and
do
not
metastasize;
unless
resected,
they
kill
by
suffocation.
TABLE 15-12 -- Local Effects of Lung Tumor Spread
Clinical Feature

Pathologic Basis

Pneumonia, abscess, lobar collapse Tumor obstruction of airway

Lipoid pneumonia

Tumor obstruction; accumulation of cellular lipid in foamy macrophages

Pleural effusion

Tumor spread into pleura

Hoarseness

Recurrent laryngeal nerve invasion

Dysphagia

Esophageal invasion

Diaphragm paralysis

Phrenic nerve invasion

Rib destruction

Chest wall invasion

SVC syndrome

SVC compression by tumor

Horner syndrome

Sympathetic ganglia invasion

Pericarditis, tamponade

Pericardial involvement

SVC, superior vena cava.

The outlook is poor for most patients with lung carcinoma. Despite all efforts at early diagnosis by frequent
radiologic examination of the chest, cytologic examination of sputum, and bronchial washings or brushings

and the many improvements in thoracic surgery, radiation therapy, and chemotherapy, the overall 5-year
survival rate is only 15%. In many large clinics, not more than 20% to 30% of lung cancer patients have
lesions sufficiently localized to even permit resection. In general, the adenocarcinoma and squamous cell
patterns tend to remain localized longer and have a slightly better prognosis than do the undifferentiated
cancers, which are usually advanced by the time they are discovered. The survival rate is 48% for cases
detected when the disease is still localized. Only 15% of lung cancers are diagnosed at this early stage, some
of which can be cured by lobectomy or pneumonectomy. Late-stage disease is usually treated with palliative
chemotherapy and/or radiation therapy. Treatment of patients with adenocarcinoma and activating mutations
in EGFR with inhibitors of EGFR prolongs survival. Many tumors that recur carry new mutations that generate
resistance to these inhibitors, proving that these drugs are hitting their target. In contrast, activating KRAS
mutations appear to be associated with a worse prognosis, regardless of treatment, in an already grim
disease. Untreated, the survival time for patients with small-cell carcinoma is 6 to 17 weeks. This cancer is
particularly sensitive to radiation therapy and chemotherapy, and potential cure rates of 15% to 25% for
limited disease have been reported in some centers. Most patients have distant metastases at diagnosis.
Thus, even with treatment, the mean survival after diagnosis is only about 1 year.
Paraneoplastic Syndromes.
Lung carcinoma can be associated with several paraneoplastic syndromes [158] ( Chapter 7 ), 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, 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. The carcinoid syndrome is more common with
carcinoid tumors, described later, and is only rarely associated with small cell carcinoma. However, small cell
carcinoma occurs much more commonly; therefore, one is much more likely to encounter carcinoid syndrome
in these patients.
Other systemic manifestations of lung carcinoma include the Lambert-Eaton myasthenic syndrome ( Chapter
27 ), in which muscle weakness is caused by auto-antibodies (possibly elicited by tumor ionic channels)
directed to the neuronal calcium channel[158]; peripheral neuropathy, usually purely sensory; dermatologic
abnormalities, including acanthosis nigricans ( Chapter 25 ); hematologic abnormalities, such as leukemoid
reactions; and finally, a peculiar abnormality of connective tissue called hypertrophic pulmonary
osteoarthropathy, associated with clubbing of the fingers.
Apical lung cancers in the superior pulmonary sulcus tend to invade the neural structures around the trachea,
including the cervical sympathetic plexus, and produce a group of clinical findings that includes severe pain in
the distribution of the ulnar nerve and Horner syndrome (enophthalmos, ptosis, miosis, and anhidrosis) on
the same side as the lesion. Such tumors are also referred to as Pancoast tumors.
NEUROENDOCRINE PROLIFERATIONS AND TUMORS
The normal lung contains neuroendocrine cells within the epithelium as single cells or as clusters, the
neuroepithelial bodies. While virtually all pulmonary neuroendocrine cell hyperplasias are secondary to airway
fibrosis and/or inflammation, a rare disorder called diffuse idiopathic pulmonary neuroendocrine cell

hyperplasia seems to be a precursor to the development of multiple tumorlets and typical or atypical
carcinoids.
Neoplasms of neuroendocrine cells in the lung include benign tumorlets, small, inconsequential, hyperplastic
nests of neuroendocrine cells seen in areas of scarring or chronic inflammation; carcinoids; and the (already
discussed) highly aggressive small cell carcinoma and large cell neuroendocrine carcinoma of the lung.
Neuroendocrine tumors are classified separately, since there are significant differences between them in
incidence, clinical, epidemiologic, histologic, survival, and molecular characteristics. For example, in contrast
to small cell and large cell neuroendocrine carcinomas, both typical and atypical carcinoids can occur in
patients with multiple endocrine neoplasia type 1. Also note that neuroendocrine differentiation can be
demonstrated by immunohistochemistry in 10% to 20% of lung carcinomas that do not show neuroendocrine
morphology by light microscopy, the clinical significance of which is uncertain.
Carcinoid Tumors.
Carcinoid tumors represent 1% to 5% of all lung tumors. Most patients with these tumors are younger than
40 years of age, and the incidence is equal for both sexes. Approximately 20% to 40% of patients are
nonsmokers. Carcinoid tumors are low-grade malignant epithelial neoplasms that are subclassified into
typical and atypical carcinoids. Typical carcinoids have no p53 mutations or abnormalities of BCL2 and BAX
expression, while atypical carcinoids show these changes in 20% to 40% and 10% to 20% of tumors,
respectively. Some carcinoids also show loss of heterozygosity at 3p, 13q14 (RB1), 9p, and 5q22, which are
found in all neuroendocrine tumors with increasing frequency from typical to atypical carcinoid to large cell
neuroendocrine and small cell carcinoma.
Clinical Features.
The clinical manifestations of bronchial carcinoids emanate from their intraluminal growth, their capacity to
metastasize, and the ability of some of the lesions to elaborate vasoactive amines. Persistent cough,
hemoptysis, impairment of drainage of respiratory passages with secondary infections, bronchiectasis,
emphysema, and atelectasis are all by-products of the intraluminal growth of these lesions.
Most interesting, albeit rare, are functioning lesions capable of producing the classic carcinoid syndrome, that
is, intermittent attacks of diarrhea, flushing, and cyanosis. Overall, most bronchial carcinoids do not have
secretory activity and do not metastasize to distant sites but follow a relatively benign course for long
periods and are therefore amenable to resection. The reported 5- to 10-year survival rates are 87% and 87%
for typical carcinoids, 56% and 35% for atypical carcinoids, 27% and 9% for large cell neuroendocrine
carcinoma, and 9% and 5% for small cell carcinoma, respectively.[159]
MISCELLANEOUS TUMORS
Lesions of the complex category of benign and malignant mesenchymal tumors, such as inflammatory
myofibroblastic tumor, fibroma, fibrosarcoma, lymphangioleiomyomatosis, leiomyoma, leiomyosarcoma,
lipoma, hemangioma, hemangiopericytoma, and chondroma, may occur but are rare. Benign and malignant
hematopoietic tumors, similar to those described in other organs, may also affect the lung, either as isolated
lesions or, more commonly, as part of a generalized disorder. These include Langerhans cell histiocytosis,
non-Hodgkin and Hodgkin lymphomas, lymphomatoid granulomatosis, an unusual EBV-positive B cell
lymphoma, and low-grade marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue
( Chapter 13 ).
A lung hamartoma is a relatively common lesion that is usually discovered as an incidental, rounded focus of
radio-opacity (coin lesion) on a routine chest film. The majority of these tumors are peripheral, solitary, less
than 3 to 4 cm in diameter, and well circumscribed. Pulmonary hamartomaconsists of nodules of connective
tissue intersected by epithelial clefts. Cartilage is the most common connective tissue, but there may also be
cellular fibrous tissue and fat. The epithelial clefts are lined by ciliated columnar epithelium or nonciliated
epithelium and probably represent entrapment of respiratory epithelium ( Fig. 15-47 ). The traditional term
hamartoma is retained for this lesion, but several features suggest that it is a neoplasm rather than a
malformation, such as its rarity in childhood, its increasing incidence with age, and the finding of
chromosomal aberrations involving either 6p21 or 12q14q15, indicating a clonal origin. [138]

Inflammatory myofibroblastic tumor, though rare, is more common in children, with an equal male-to-female
ratio. Presenting symptoms include fever, cough, chest pain, and hemoptysis. It may also be asymptomatic.
Imaging studies show a single (rarely multiple) round, well-defined, usually peripheral mass with calcium
deposits in about a quarter of cases. Grossly, the lesion is firm, 3 to 10 cm in diameter, and grayish white.
Microscopically, there is proliferation of spindle-shaped fibroblasts and myofibroblasts, lymphocytes, plasma
cells, and peripheral fibrosis. The anaplastic lymphoma kinase (ALK) gene, located on 2p23, has been
implicated in the pathogenesis of this tumor.
Tumors in the mediastinum either may arise in mediastinal structures or may be metastatic from the lung or
other organs. They may also invade or compress the lungs. Table 15-13 lists the most common tumors in the
various compartments of the mediastinum. Specific tumor types are discussed in appropriate sections of this
book.
TABLE 15-13 -- Mediastinal Tumors and Other Masses
SUPERIOR MEDIASTINUM
Lymphoma
Thymoma
Thyroid lesions
Metastatic carcinoma
Parathyroid tumors
ANTERIOR MEDIASTINUM
Thymoma
Teratoma
Lymphoma
Thyroid lesions
Parathyroid tumors
POSTERIOR MEDIASTINUM
Neurogenic tumors (schwannoma, neurofibroma)
Lymphoma
Gastroenteric hernia
MIDDLE MEDIASTINUM
Bronchogenic cyst
Pericardial cyst
Lymphoma
METASTATIC TUMORS
The lung is the most common site of metastatic neoplasms. Both carcinomas and sarcomas arising anywhere
in the body may spread to the lungs via the blood or lymphatics or by direct continuity. Growth of contiguous
tumors into the lungs occurs most often with esophageal carcinomas and mediastinal lymphomas.