PATHOLOGY OF THE LUNGS
1. CONGENITAL DISEASES
1. Bronchopulmonary sequestration
-normally- the lungs develop from buds arising from embryonal foregut
-occassionally- additional segment of lung develops from an abnormal
accessory lung buds- bronchi in this abnormal lung segment do not
communicate with the normal bronchial tree- this abnormal lung segment is
sequestrated
-this results in accumulation of mucous secretion - followed by
infection abscess formation- fibrosis- bronchiectasiae- dilatation of bronchi
patients present with a mass in the lung- most commonly in the left lower
lobe
2. Bronchogenic cyst
-arises from accessory bronchial buds that loses communication with
the tracheobronchial tree
the bud becomes dilated into a cyst- mucous accumulation
-the cyst is lined by respiratory epithelium- there may be a cartilage in
the wall- attachment to the trachea is retained
3. Congenital cystic adenomatoid malformation
-commonly presents in the newborn period
-it usually involves one lobe- which is enlarged
histology: affected part of the lung is composed of abnormal cystic cavities
lined by bronchiolar mucinous epithelium- these cystic masses may
compress adjacent normal lung - surgical removal of the involved lobe is
curative
4. Tracheo-esophageal fistula= abnormal communication between the
esophagus and the trachea
usually presents with cyanosis and respiratory distress at the time of first
feeding-surgical closure of the fistula is curative
5. Congenital atelectasis= neonatal respiratory distress syndrome
atelectasis= failure of the lung to expand at birth
- atelectasis is focal or may affect all of both lungs
Causes of atelectasis include
- inadequate respiratory movements in a newborn (due to neurologic
damage or severe anoxia)
- bronchial obstruction
- absence of surfactant (RDS=respiratory distress syndrome)
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-the most important is the idiopathic RDS, known also as hyaline membrane
disease pathogenesis:
- deficiency in pulmonary surfactant -surfactant includes phospholipids and
proteins that function to reduce surface tension within alveoli- facilitates
alveolar expansion
-in healthy newborn surfactant rapidly coats the surface of
alveoli with the first breath- decreased the pressure required to keep alveoli
open
- surfactant is secreted by pneumocytes II- modulated by glucocorticoids and
other hormones- after 35th week of gestation
- immaturity of lungs in preterm infants is the most important causes of
RDS
-in lungs deficient in surfactant- alveoli tend to collapse- greater
respiratory effort is required to open the alveoli in each breath
incidence: 60% at less than 28 weeks of gestation
5% at less than 37 weeks of gestation
morphologic features and pathogenesis:
-lack of surfactant-results in atelectasis-causes hypoxemia and
acidosis and pulmonary capillary damage- fibrin-rich exudate is formed
within alveoli-hyaline membranes
macroscopic appearance - the lungs are firm, solid, airless
histologically:
-in early stage-collapsed alveolar spaces are lined by fibrin-rich hyaline
membranes with necrotic debris-within bronchiloes and alveoli
later-reparative and proliferative changes including interstitial fibrosis
and hyperplasia of pneumocytes II
clinical features:
-the prognosis of RDS- depends on maturity of the infant
overall mortality is high- up to 20 to 30%- the most common complications
include
-chest diffuse interstial fibrosis and cerebral intraventricular
hemorrhage
2. PULMONARY VASCULAR DISORDERS
1. Adult respiratory distress syndrome ARDS = shock lung
= is characterized by diffuse alveolar capillary damage leading to severe
respiratory failure and arterial hypoxemia
the major causes of ARDS include:
-septic shock
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-shock associated with trauma, tumors and complicated surgical
procedures
-diffuse pulmonary infections
-inhalation of toxins
respiratory failure is unresponsive to oxygen therapy- over 50% mortality
histology and pathogenesis:
- initially the basic lesion affects capillary endothelium-the damage to the
capillary endothelium results in an increased capillary permeability-edema
and fibrin exudation folowed by formation of hyaline membranes - composed
of necrotic epithelial cell debris and exudative proteins-predominantly fibrin
the other characteristic morphologic feature - inflammatory infiltration of the
interalveolar septa
mechanisms and events involved in this injury include:
-oxygen-derived free radicals -(especially in the toxicity produced by
long lasting exposure to high-concetration of oxygen) - causes capillary
damage and aggregations of activated leukocytes- in the pulmonary vessels-
these activated neutrophils may secrete various mediators and injurious
factors, such as radicals, lysosomal enzymes, etc.
-loss of surfactant- leading to atelectasis resulting in typical
appearance of the lungs in ARDS- stiff, firm, airless
morphology:
-in acute stage- the lungs are diffusely firm, stiff, heavy
histologically-edema, hyaline membranes, acute inflammation of
interalveolar septa
-in later stage- signs of proliferation and organization
-patchy areas of organization-interstitial fibrosis
- and type II pneumocytes proliferation
frequently with superimposed bacterial infection in fatal cases
clinical features: -patients with ARDS are often seriously ill- with other
severe primary disease and the features of ARDS are superimposed - ARDS
is commonly a terminal event
respiratory symptoms of ARDS include:
-rapidly progressing dyspnea
-hypoxemia and cyanosis
these usually occur 1-2 days after the onset of acute injury or disease that
has become complicated by ARDS
-chest x-ray shows diffuse interstitial or alveolar edema
2. Pulmonary embolism-pulmonary emboli originate from deep leg veins in
over 90% of cases, pelvic veins are second in frequency
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-very common immediate cause of death
thromboembolism occurs most commonly
-occurs as a terminal complication in patients after surgery
-in patients after surgery
-after childbirth
-in patients who are immobilized for any reason ( bone fracture)
-in patients with cardiavascular diseases such as myocardial
infarctions or congestive heart failure
-in women receiving oral contraceptives higher risk of
thromboembolism
clinical symptoms associated with pulmonary embolism:
-sudden death -may occur with a large embolus that becomes
impacted in the right ventricular outflow tract or main pulmonary artery-so
called saddle embolus
blood circulation is effectively obstructed-followed by heart failure-cor
pulmonale acutum
-pulmonary infarction-occurs when a medium-sized peripheral artery is
obstructed by embolus- in patients whose bronchial arterial circulation is
also impaired- such as in patients with left heart failure or pulmonary
hypertension
- pulmonary infarcts are hemorhagic (red), wedge-shaped with the base at
the pleura and apex directed toward the occluded vessel
microscopically- alveolar necrosis and hemorrhage is present, pulmonary
infarcts heal by fibrosis- subpleural scar
clinically-the patients present with chest pain, fever, hemoptysis
(hemorrhagic pleural effusion)
pulmonary hypertension-multiple small emboli over a long period may cause
diffuse alveolar fibrosis and pulmonary hypertension
3. Pulmonary Hypertension
=elevation ot the mean pulmonary arterial blood pressure-secondary
hypertension
most common cause include: mitral valve disease, left ventricle heart failure,
congenital heart diseases with left to right shunt, atrial septal defects
-chronic pulmonary diseases, such as bronchitic emphysema,diffuse
interstitial fibrosis, multiple recurrent pulmonary emboli
in small number of patients-no recognizable cause of PH = primary pulmonary
hypertension
-.mainly in young women (2.-3 dec.), frequently associated with
rheumatoid arthritis or other immunologically medited collagen disorders
pathology of PH: similar in primary and secondary PH
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-fibrous thickening of pulmonary arteries of all sizes with medial
hypertrophy and atherosclerosis (not found in patients without PH)
-abnormal plexiform arteriolar structures
clinically: causes right ventricular hypertrophy- RV failure followed by
peripheral edema-
- primary hypertension is slowly progressive but irreversible
secondary- the cause may be treated-prevention of progression of
hypertension
3. OBSTRUCTIVE LUNG DISEASES
-all obstructive lung diseases are characterized by an increased
resistence to airflow-due to complete or partial obstruction at any level
-major obstructive diseases are such as asthma., chronic brinchitis,
emphysema, bronchiectasie, cystic fibrosis, bronchiolitis
1. emphysema
= abnormal enlargment of air spaces distal to the terminal bronchioles
accompanied by destruction of their walls
-in contrast,there are several conditions in which enlargement of
airspaces is not associated with destruction- overinflation- for example after
unilateral lobectomie
-emphysema is classified according to the anatomic location of the lesion
-normal acinus consists of respiratory bronchile-alveolar duct- and alveolus
centriacinar(centrilobular)-destruction of central parts of acini sparing
distal alveoli
-this lesion is more common and severe -in upper lobes
-male smokers, often in chronic bronchitis
panacinar-uniform enlargement and destruction of the whole acini
-mpre commonly occurs in lower basal lung zones
-association with alfa-1-antitrypsin deficiency
paraseptal(distal acinar) - in this form the proximal portion of
thealveolus is normal but the distal part is affected
-more string adjacent to pleura, along scars, and fibrous septa, etc.
-may result in pneumothorax
irregular- in old persons, usually asymptomatic
incidence: emphysema is common disease, in autopsy series the numbers
vary between 25% (in women) and 60% (in men)-most cases are
asymptomatic
pathogenesis of the two most common types (centriacinar and panacinar) is
unclear
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protease-antiprotease hypothesis says that in emphysema- there is an
imbalance between proteases and their inhibitors, such as alfa-1-antitrypsin
evidence-experimental-installation of proteolytic solutions leads to
emphysema
-pateints with genetic alfa-1-antitrypsin deficiency-enhanced tendency
for developing emphysema
tobacco smoking contribution- in smokers- alveoli contain many smoke-
activated macrophages- they release promoting factors that activate
neutrophils and stimulate release of elastase from these neutrophils-with
low level of alfa-1-antitrypsin, elastic tissue destruction is uncontrolled-
emphysema results
diagnosis and morphology of emphysema:
-grossly-enlargement of the lung, most impressive in panacinar
emphysema
-histologically: thinning and destruction of interalveolar walls-
adjacent alveoli become confluent, creating large alvolar spaces
clinical course:
-dyspnea is the first symptom -in patients without bronchitis- steadily
progressive disease-prolonged expiration-hyperventilation may be
prominent-expiratory effort-weight loss is common
-in patients with underlying chronic bronchitis and asthma- cough
and wheezing-less prominent dyspnea and not increased ventilation-the
patients retain carbon dioxide- become cyanotic-tned to be obese for
unknown reasons-congestive heart failure
conditions related to emphysema:
-compensatory emphysema-is dilatation of alveoli in response to loss of
lung parenchyma- more appropriate term is overinflation
-senile emphysema-refers to overdistended lungs of older persons-no
significant tissue destruction-better term would be senile hyperinflation
-obstructive overinflation-refers to the situation of entrapment of the
aier within the lung with subsequent distention-occurs in subtotal
obstruction- ball-valve effect- inspiration is possible but not expiration or
occurs in total obstruction- inspiration is possible through collaterals
-bullous emphysema - refers to any emphysema that produces large
bullae (spaces more than 1 cm in diameter)
2. Chronic bronchitis
-characterized as clinically persistent cough with sputum production
for at least 3 months in at least 2 consecutive years
morphologically it is characterized by:
-mucinous secretion or casts filling airways
-hyperplasia of mucous glands
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-squamous metaplasia and dysplasia of bronchial epithelium
-hyperemia and edema of mucous membranes of lungs
-infections are a secondary factor that maintain and promote lung injury
clinical course: the patients have prominent cough and production of
sputum- ventilatory dysfunction-chronic obstructive pulmonary disease-
hypoxemia and hypercapnia, cyanosis-cor pulmonale chronicum-recurrent
infections and respiratory failure
3. Bronchial astma
=disease characterized by paroxysmal contraction of bronchial airways
caused by increased responsiveness to various stimuli
two major types of astma
-extrinsic factors- caused by allergens
-intrinsic factors-idiopathic
1.-allergic ( atopic ) astma- the most common type
-caused by extrinsic allergens, such as dust, food, bacteria, etc.
it is a classic type I IgE-mediated hypersensitivity reaction
-in acute phase- binding of antigen by IgE-coated mast cells- release of
primary mediators (=histamine, chemotactic factors) andsecondary
mediators, such as PAF, leukotrienes, prostaglandin D2
-activity of these acute phase-mediators result in
-bronchospasm, edema, mucous secretion and recruitment of leukocytes
-late- phase reaction- mediated by leukocytes
-characterized by persistent bronchospasm, edema, leukocytic infiltration,
necrosis of epithelial cells
2.-non-atopic astma -trigerred by respiratory tract infections, chemical
irritants, drugs, with little or no evidence of IgE-mediated hypersensitivity
morphology in bronchial astma:
grossly:-the lungs are overinflated, patchy atelectasis
some airways are occluded by mucous plugs
microscopically:
-edema, inflammatory infiltration of bronchial walls ( mostly
eosinophilic infiltration )
-hypertrophy of muscular layer of bronchial walls
-presence of whorled mucous plugs (Curschman spirals) and crystalloid
debris in the sputum (Charcot-Leyden crystals)
clinical course: -asthma attack is characterized by severe dyspnea with
wheezing- chief problems with expiration-there is progressive hyperinflataion
of the lung with air entrapped within alveoli- therapy includes
bronchodilatators and corticosteroids
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status asthmaticus- severe paroxysm lasting several days that do not
respond to therapy-severe hypoxia, acidosis- may be fatal
4. Bronchiectasis = abnormal dilatation of terminal airways associated with
chronic necrotizing infection of bronchi and bronchioles
clinical features: cough, fever, purulent sputum
-later is complicated by cor pulmonale, systemic amyloidosis or
metastatic abscesses
-bronchiectasis is seen in association with bronchial obstruction, for
example due to tumors
-congenital-in cystic fibrosis, in lung sequestrations
-in Kartagener syndrome-immobile cilia syndrome
-in necrotizing pneumonia
4. RESTRICTIVE LUNG DISEASES
=heterogenous group of lung diseases that are characterized by
reduced compliance- it means that more pressure is required to expand the
lungs
-restrictive lung diseases are heterogenous- as to the cause and
pathogenesis
-they have similar clinical signs and symptoms, similar rtg findings,
similar pathophysiologic changes:
-clinically severe dyspnea and decreased lung volume
-pathologically-diffuse chronic infiltration and fibrosis of alveolar
interstitium-because of prominent changes in the intersitium- they are
referred to as chronic interstitial diseases of the lungs
-interstitial fluid or fibrosis produces a stiff lung -which necessitates
increased effort of breathing
-damage to the epithelium and interstitial vasculature produces
abnormalities in ventilation and perfusion- resulting in hypoxia
pathogenetic events:
initial- injury to epithelium and endothelium
-early acute changes- alveolitis consisting of activated inflammatory
cells within alveolar walls - these cells release cytokines (injury)-meditors with
fibrogenic effects- mediators such as PDGF, FGF, Interleukin 1
-late phase- destruction of pulmonary substance and fibrosis
-restrictive lung disease can be either acute-or-chronic
1.-acute-most important- ARDS- Adult respiratory distress syndrome-
diffuse alveolar damage
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2.-chronic-most common -caused by environmental agents, like
aerosols with mineral dusts, organic dusts, fumes and vapors- result in
pneomoconioses (25 %)
-infections-sarcoidosis,
-of unknown etiology- idiopathic pulmonary fibrosis,
hypersensitivity pneumonitis, pulmonary eosinophilia, bronchiolitits
obliterans, diffuse pulmonary hemorrhage, pulmonary alveolar proteinosis,
-and complications of therapy- such as drug-induced lung
disease and radiation-induced lung disease
Chronic restrictive pulmonary diseases include:
1) idiopathic pulmonary fibrosis - hamman-rich
-chronic progressive lung disease of unknown etiology characterized by
progressive pulmonary interstitial fibrosis-resulting in hypoxemia
-most common in males between 30 and 50
morphologic changes:
-early- interstitial and intra-alveolar edema
interstitial infiltration and proliferation of type II pneumocyte
-end-stage- interstitial and intraalveolar fibrosis
the lung consists of spaces lined by epithelium and separated by
inflammatory fibrous tissue=honeycomb lung
-the disease is progressive- chronic pulmonary insuficiency- cor pulmonale -
cardiac failure
2) hypersensitivity pneumonitis
-immunologically mediated lung disorder caused by inhaled dusts or
antigens-most often occupational disease, such as
-farmers lung- caused by spores of actinomycetes in hay
-pigeon breeders lung-caused by proteins from birds feather
histologic changes:
-interstitial pneumonitis and fibrosis
-presence of noncasating epithelioid granulomas
clinical- cough, dyspnea, fever, restrictive pattern of lung dysfunction
3) pulmonary eosinophilia
-group of clinicopathologic conditions characterized by massive
infiltration of the pulmonary interstitium by eosinophils
-1-simple pulmonary eosinophilia- Loeffler’s syndrome
characterized by transient benign eosinophilic infiltrates with prominent
blood eosinophilia- unclear pathogenesis
-2-secondary chronic pulmonary eosinophilia-
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which is induced by infections-aspergillosis, by asthma, etc.
-3-idiopathic chronic eosinophilic pneumonia
disorder of unknown etiology, manifested by focal consolidation of lung with
prominent eosinophils and lymphocytes
4) pulmonary alveolar proteinosis
-disease of unknown etiology and pathogenesis characterized by
accumulation of dense, PAS-positive lipid-laden macrophages in alveoli
-the intralveolar exudate consists of surfactant-like material, necrotic
alveolar macrophages and type II pneumocytes
-the disease may occur after exposure to irritating dusts and in
immunosupressed persons
it is progressive in many cases-clinically - respiratory difficulty, cough and
sputum
5) diffuse pulmonary hemorrhage
-serious complication of some interstitial lung diseases
so-called pulmonary hemorrhage syndrome includes two clinicopathologic
entities
1- Goodpasture syndrome
-necrotizing hemorrhagic interstitial pneumonitis associated with
progressive glomerulonephritis- caused by antibodies against analogous
basement membranes antigens both in lungs and kidneys
2- Idiopathic pulmonary hemosiderosis
-chronic, episodic hemorrhages to the lungs- of unknown etiology
results in hemosiderosis, fibrosis and chronic cardiorespiratory failure
5. INFECTIONS OF THE LUNGS
-occur when normal lung or systemic defense mechanisms are
impaired
-pulmonary defense-include nasal and tracheobronchial mechanisms
to filter and clear inhaled organisms and particles
important factors interfering with normal lung defenses are
-loss of cough reflex leading to possible aspiration
-injury to mucociliary apparatus (caused for example by cigarette
smoking)
-decreased phagocytic function of the alveolar macrophages (tobacco,
alcohol, oxygen toxicity)
-edema and congestion, for example in cardiac failure
-by accumulation of secretions
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1. Bacterial pneumonia
-occurs in two overlapping morphologic patterns-as bronchopneumonia and
lobar pneumonia -can be caused by variety of organisms, most commonly
staphylococci, streptococci, pneumococci, Heamophilus influenzae and
Pseudomonas aeruginosa
Bronchopneumonia-is characterized by patchy exudative consolidation of
lung parenchyma
Grossly: the lungs show dispersed focal areas of palpable consolidation and
suppuration-whitish yellow in color
histologic features consist of an acute suppurative exudate ( neutrophilic)
filing air spaces-bronchioles and alveoli
-resolution of the exudate-usually to normal lung structure, but
organization may occur ( lung carnification) resulting in scar formation
in more aggressive cases- formation of abscesses
Lobular pneumonia-is characterized by involvement of large portion of or an
entire lobe of lungs
-classic stages of lobular pneumonia- are not seen nowadays because
of antibiotic therapy
-1-congestion-in the first 24 hours
-2-red hepatization-acute exudation containing neutrophils and RBCs-
red, firm, liver-like appearance
-3-gray hepatization- RBCs have desintegrated, fibrino-suppurative
exudate persists, giving a gray-brown gross appearance, firm consistency
-4-resolution-consolidated exudate undergoes enzymatic digestion-
normal structures are restored, but usually- organization and scar formation
2. Viral and mycoplasmal ( primary, atypical) pneumonia
infections by viruses ( influenza A or B, respiratory syncytial virus,
adenovirus, rhinovirus, herpes simplex) or Mycoplasma pneumoniae
-relatively mild upper respiratory tract involvement ( common cold) to
severe lower respiratory tract disease
morphology: patchy or lobar areas of congestion without the consolidation (
hence the term „atypical“)
histology: interstitial infiltration- edematous widened interalveolar septa
formation of hyaline membranes- diffuse alveolar damage
frequently superimposed bacterial infections
3. Tuberculosis
-chronic infectious disease caused by Mycobacterium tuberculosis,
characterized by specific necrotizing (caseating) granulomas
- there are two major forms of tuberculosis depending on the individual
hypersensitivity and resistence
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1-Primary pulmonary tuberculosis
-this form occurs in individuals lacking previous contact with
tuberculous bacilli
the disease begins as a single granulomatous lesion-subjacent to pleura in
the lower upper lobe region- primary lesion (consolidated focus of
granulomatous inflammation)-also known as Ghon focus,
-tbc bacilli can be demonstrated histologically with acid-fast stains in
early lesions, old scarrred tubercles may have no visible organism but
contain them even afetr decades in latent form- may be under caerain
circumstances reactivated
in addition to primary lesion, in most cases there is spread to draining
bronchial or hilar lymph node - granulomatous inflammation of these
nodes,
combination of primary lung lesion and lymph node tbc is known as Ghon
complex - primary complex
in most cases the infection does not progress- results in local scarring and
calcification
-infrequently- primary tbc may progress- with enlargment of the
inflammatory focus this is tbc pneumonia- possible cavitation, or/nad
erosion of the bronchial wall- with a danger of spread of infection within
the whole lung
-further complication- is miliary tbc- bloodstream dissemination
2-Secondary pulmonary tuberculosis
-this term denotes active tbc infection in a previously sensitized
individual
-most cases represent endogenous reactivation of dormant bacilli from the
primary lesions
occassionally- exogenous sources of tbc cause secondary tuberculosis
-secondary tbc is usually found in the apices of the lungs-these lesions may
progress- cavitary fibrocaseous tbc, tbc bronchopneumonia or miliary tbc
Clinical features:
primary tbc is usually asymptomatic, the secondary form more often causes
fever, night sweats, weight loss, productive cough with hemoptysis
-diagnosis relies on demonstration of acid-fast bacilli in sputum or in
biopsy
Prognosis: is variable, depending on the extent of disease, health condition of
the patients, and aggressiveness of tbc bacilli
Disseminated tuberculosis
-hematogenous spread of tbc bacilli may produce two patterns
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1-miliary tuberculosis-multiple minute foci of infection in many organs, such
as lungs, liver, bine marrow,kidney, spleen, etc
2-isolated organ tuberculosis-large focus or several foci in one or two organs,
most often- kidneys , bone (tbc osteomyelitis), female genital tract (salpingitis,
endometritis)
6. TUMORS OF LUNGS
1. Bronchogenic carcinoma -most important lung tumor, accounts for about
90% of lung tumors
-most common cause of cancer death in men
pathogenesis:
tobacco smoking is well established supplementary factor in developing the
lung cancers-there are statistical, clinical and experimental indicators of
this link between tobacco smoking and lung cancer
-statistically- direct association between the frequency of lung cancer
and numbers of packs and numbers of years of smoking
-clinically- hyperplasia and dysplasia may be seen in the bronchial
epithelium in smokers
-experimentally- numerous known carcinogens in cigarette smoke
the other etiologic factors include- radiation (uranium miners, atomic
bomb survivors), exposure to asbestos (especially if combined with
cigarette smoking)
Histologic types of bronchogenic carcinoma:
a) squamous cell carcinoma
-closest relation with smoking- 98%of patients are smokers
-most commonly arises within or near the hilus of the lung
-more common in men
microscopically broad spectrum-vary from well-differentiated keratinizing
tumors to anaplastic carcinomas with only focal squamous differentiation
b) adenocarcinoma
-equal frequency in men and women,
-often presents as peripherical mass-sometimes in subpleural scars
histologically-tumor is composed of glandular structures with mucin
production
c) small cell carcinoma
-the most common type, most malignant
-often presents as central or hilar tumor
-strongly associated with smoking-99% of patients are smokers
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microscopically- it is characterized by small, oat-like cells with little
cytoplasm-similar to lymphocytes, without squamous or glandular
differentiation
-some cancer cells may reveal neurosecretory features (cytoplasmic
neurosecretory granules, immunohistochemical positivity with antibodies to
serotonin, synaptophysin, neurone specific enolase, chromogranin, etc)
paraneoplastic syndromes:
-often stem from the release of hormones, such as antidiuretic
hormone - ADH syndrome
-adrenocorticotropic hormone - Cushing’s syndrome
-parathormone-hypercalcemia
-calcitonin-hypocalcemia
-serotonin - carcinoid syndrome
prognosis: poor, median survival for untreated patients is 3 months, with
combination chemotherapy and chest radiotherapy-the median survival is
10-16 months with limited stage of disease and 6-10 months for patients in
extensive stage disease
-6-13 % patients survive 2 and more years, about 5% survive 10 years
d) large cell carcinoma and other types
-large cell carcinoma is composed of large cells without squamous
differentiation, without gland formation, and mucin production
-usually large necrotic tumor invading the pleura and other organs
prognosis and therapy is similar with small cell carcinoma-poor
2. Bronchioalveolar carcinoma
-uncommon form of adenocarcinoma arising in terminal bronchioles
-always in the lung periphery
histologically: there are two distinctive variants of BAC:
type I BAC- tumor cells are tall, often mucin-producing, they line well
preserved alveolar septa, forming papillary projections into the alveolar
spaces
type II BAC- arises from pneumocytes of type II- non-mucinous type BAC
tumor cell are mucin-negative, immunohistochemically- tumor cells express
surfactant apoprotein
-better prognosis than type I BAC- because mucinous BACs tend to be larger
clinically: the frequency is equal for men and women, it is not associated
with smoking
treatment and prognosis: generally better than that of adenocarcinoma,
resection is curative,
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in early stage disease prognosis is excellent- with 5-year survival of 90%, in
advanced stage- prognosis is similar to that of adenocarcinoma
3. Bronchial carcinoid
-less common lung tumor, represents 1 to 5 % of all lung tumors
-low-grade malignant tumors, that can be divided into typical and
atypical subtypes- the latter possess more malignant clinical features
-carcinoid is characterized by neuroendocrine differentiation-some
tumors may be endocrinologically silent, but other cases show secretion of
serotonin and 5-hydroxytryptophan (ultrastructurally neurosecretory
granules)
three major forms of pulmonary carcinoid tumor include
1-central carcinoid tumor
-most common type, presents as slowly growing solitary intrabronchial
polypoid mass
microscopically: highly vascularized, composed of uniform small round cells
in cords and nests- resemble intestinal carcinoids
prognosis:usually good prognosis
only about 10% of these tumors show aggressive behavior, in most cases
surgical resection is curative
2- peripheral carcinoid tumor
-arises in the peripheral lung, often immediately beneath the pleura, is
composed of spindle-shaped cells
- better prognosis-most peripheral carcinoids are typical
3-atypical carcinoid tumor
-structure as in classical central carcinoid, but increased mitotic activity,
foci of necrosis, cellular polymorphism
-much worse prognosis- the treatment should be more aggressive - this
tumor is related to small-cell carcinoma of the lung
treatment of carcinoid tumors: surgery is the primary management, lymph
node sampling is necessary, because all carcinoids have potential to lymph
node metastases
-atypical carcinoids- are larger if compared with typical, higher rate of
metastases, significantly reduced survival- mean survival is about 2 years (
in typical carcinoids-according to one study 5-year and 10-year survival are
100% and 87%, respectively)
4. Epithelioid hemangioendothelioma
-is an uncommon lung tumor-represents a low-grade sclerosing
angiosarcoma-usually presents as multiple small nodules in both lungs
-more often in young women
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-it was originally thought that this tumor is an unusual variant of
bronchioalveolar tumor with an intravascular spread, thus it was originally
referred to as IVBAT ( Intravascular bronchoalveolar tumor)
microscopically: the tumor consists of central necrosis and cellular periphery
composed of polymorphous cells lining preserved alveolar spaces
-tumor cells show endothelial differential- intracytoplasmic lumina, positive
stain for factor VIII-related antigen,etc
therapy is difficult- prognosis is variable- some cases progress very slowly-
with survival of 20 years and more- whereas others rapidly lead to death in
respiratory failure- radiotherapy is uneffective
5. Chondrohamartoma
relatively common, entirely benign,
grossly: presents as solitary, well-circumscribed nodular tumor- firm
cartilaginous consistency
-histologically-composed of cartilage, fibrous tissue, blood vessels, fat and
spaces lined by respiratory epithelium
6. Sclerosing hemangioma of the lung
-is unusual benign pulmonary tumor, that was described as
hemangioma because of presence of large hemorhagic areas and spaces
often filled with erytrocytes-that were considered vascular
-grossly: this tumor often presents as a solitary round-shaped mass in
subpleural location
-occurs in all ages, more than 80% of patients are women
histogenesis: despite the name - tumor is of epithelial origin-tumor cells
express cytokeratins and do not show positivity for endothelial markers, in
addition, there is surfactant apoprotein in the cytoplasm of tumor cells-
these arise from pneumocytes type II
microscopically this tumor consists of solid cellular portions admixed with
papillary and angiomatous structures, hemorrhages and deposits of
hemosiderin are typical features
-focal sclerosis is common, aggregates of foamy macrophages may be
present prognosis is very good-surgical excision is curative
7. Inflammatory pseudotumor-Plasma cell granuloma-histiocytoma complex
-is well circumscribed, usually single, tumorous lesion that destroys
lung architecture -benign tumor or lesion of reactive inflammatory origin-
sometimes called inflammatory pseudotumor
grossly: well circumscribed lesion of firm consistency, central necrosis, may
achieve even 20 cm in diameter
microscopically: composed of variable mixture of collagen, polymorphous
inflammatory cells, and elongated spindle cells of myofibroblastic and
fibroblastic nature
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-patients range in age from children up to 70 years, but most commonly
affected persons are about 40 years of age
-most patients present with cough, fever, chest pain, hemoptysis, shortness
of breath
prognosis: this tumor is probably best to be treated by surgery, there are
however reports of partial resection followed by spontaneous disappearance,
and corticosteroid-therapy may be effective
.in other cases- the tumor may grow slowly or even rapidly, can invade
pulmonary veins, pleura or even mediastinum-more aggressive lesions may
cause death
METASTATIC TUMORS IN LUNGS
-the lung is one of the most frequent sites of metastatic disease
most metastases- multiple, sharply outlined, rapidly growing
most common primary tumors - carcinoma of breast, stomach
isolated metastasis in lung- may closely simulate primary lung cancer- well
known situation for primary clear-cell carcinoma of kidney, less commonly
for primary testicular tumors
TUMORS OF THE PLEURA
1. Benign mesothelioma
-mesothelioma is a tumor derived from the lining cells of a serous
cavity (mesothelium)
-localized, non-invasive tumor, which is relatively common in the peritoneal
cavity, but rare in the pleura
-is composed of papillary processes lined by one or several layers of cuboidal
mesothelial cells- the distinction with malignant mesothelioma is made on
basis of the lack of atypia and solitary well circumscribed nature of this
tumor
grossly: it presents as soft friable gray to yellow mass-is confined to a single
area
resection is curative
2. Malignant mesothelioma
-rare tumor of mesothelial surface that infiltrates in diffuse pattern
-occurs most often on the pleura, rarely on the pericardium and peritoneum
may be associated with exposure to asbestos
morphology: the tumor spreads diffusely on the surface of the lungs,
extension into the subpleural portion of the lung is also common
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microscopically, it is characterized by biphasic growth pattern, composed of
sarcomatoid formations- malignant spindle-shaped cells- resemble
fibrosarcoma
and of epithelioid growth composed of epithelium-like cells forming tubules,
papillary projections
clinically: highly malignant-invade the lung and widely metastasize
the patients present with chest pain, dyspnea, pleural effusions
prognosis of pleural mesothelioma is uniformly poor
3. Solitary fibrous tumor of pleura (so-called localized fibrous mesothelioma)-
benign tumor
-it arises from subpleural mesenchymal cells normally present
subjacent to basement membrane of mesothelium
-is always well circumscribed
-it is asymptomatic, or on occasion the patients may present with
pain, cough and dyspnea -not associated with asbestosis
microscopically:- the tumor is composed of network of slender fibroblasts
accompanied by deposits of dense collagen fibres
-no mitoses -very good prognosis- treated by simple resection
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