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)
1
-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
RDS
- immaturity of lungs in preterm infants is the most important causes of
-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
hemorrhage
diffuse
interstial
fibrosis
and
cerebral
intraventricular
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
2
-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 vesselsthese activated neutrophils may secrete various mediators and injurious
factors, such as radicals, lysosomal enzymes, etc.
-loss of surfactant- leading to atelectasis
appearance of the lungs in ARDS- stiff, firm, airless
resulting
in
typical
morphology:
-in acute stage- the lungs are diffusely firm, stiff, heavy
histologically-edema,
interalveolar septa
hyaline
membranes,
acute
inflammation
of
-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
3
-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
infarctions or congestive heart failure
-in
women
thromboembolism
receiving
oral
diseases
such
contraceptives
as
higher
myocardial
risk
of
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
(hemorrhagic pleural effusion)
with
chest
pain,
fever,
hemoptysis
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
4
-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
hypertension
cause
may
be
treated-prevention
of
progression
of
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
5
protease-antiprotease hypothesis says that in emphysema- there is an
imbalance between proteases and their inhibitors, such as alfa-1-antitrypsin
evidence-experimental-installation
emphysema
of
proteolytic
solutions
leads
to
-pateints with genetic alfa-1-antitrypsin deficiency-enhanced tendency
for developing emphysema
tobacco smoking contribution- in smokers- alveoli contain many smokeactivated 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 uncontrolledemphysema results
diagnosis and morphology of emphysema:
-grossly-enlargement of the lung, most impressive in panacinar
emphysema
-histologically: thinning and destruction of interalveolar
adjacent alveoli become confluent, creating large alvolar spaces
walls-
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
6
-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 diseasehypoxemia 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
eosinophilic infiltration )
infiltration
of
bronchial
walls
(
mostly
-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
7
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 effectsmediators 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 syndromediffuse alveolar damage
8
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
etiologyidiopathic
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-
9
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
10
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 RBCsred, 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 digestionnormal 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
characterized by specific necrotizing (caseating) granulomas
tuberculosis,
- there are two major forms of tuberculosis depending on the individual
hypersensitivity and resistence
11
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
12
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
13
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,
14
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
15
-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 slowlywith 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 cellsthese 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 originsometimes 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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