Top ic: PATH OLOGY Lun gs (Pulm ona ry In fe ctio ns an d Tumo rs )

Lec turer: D r. R. E. Ecl arin

Date : N ove mbe r 18, 2016
Trans cribe d by: Cas tro , G.| Cond e| Raymun do |Reb lan do| Sa ldu a
OUTLINE
I. Pulmonary Infections
A. Community-Acquired Bacterial Pneumonias
1. Streptococcus pneumoniae
2. Haemophilus influenza
3. Moraxella catarrhalis
4. Staphylococcus aureus
5. Klebsiella pneumonia
6. Pseudomonas aeruginosa
7. Legionella pneumophila
8. Mycoplasma pneumonia
B. Community-Acquired Viral Pneumonia
1.
Influenza Infections
2.
Human Metapneumovirus
3.
Severe Acute Respiratory Syndrome
C. Health Care-Associated Pneumonia
D. Hospital-Acquired Pneumonia
E. Aspiration Pneumonia
F. Lung Abscess
G. Chronic Pneumonia
a.
Histoplasmosis
b.
Blastomycosis
c.
Coccidioidomycosis
H. Pneumonia in the Immunocompromised Host
I. Pulmonary Disease in Human Immunodeficiency Virus Infection
II. Tumors
A. Carcinomas
B. Neuroendocrine Proliferations and Tumors
C. Miscellaneous Tumors

PULMONARY INFECTIONS
Impared local defense mechanismor lowered
systemic resistance of the host
o Chronic diseases, immunologic deficiency,
treatment with immunosuppressive
agents, and leukopenia
Loss or suppression of the cough reflex as a result
of coma, anesthesia, neuromuscular disorders,
drugs, or chest pain (may lead to aspiration of
gastric contents)
Injury to the mucociliary apparatus by either
impairment of ciliary function or destruction of
ciliated epithelium, due to cigarette smoke,
inhalation of hot or corrosive gases, viral diseases,
or genetic defects of ciliary function (e.g., the
immotile cilia syndrome)
Accumulation of secretions in conditions such as
cystic fibrosis and bronchial obstruction

Interference with the phagocytic or bactericidal

action of alveolar macrophages by alcohol,
tobacco smoke, anoxia, or oxygen intoxication
Pulmonary congestion and edema

Community-Acquired Bacterial Pneumonia
Lung infection in otherwise healthy individuals
that is acquired from the normal environment
Bacterial invasion of the lung parenchyma causes
the alveoli to be filled with an inflammatory
exudate,
thus
causing
consolidation
(solidification) of the pulmonary tissue
Specific etiologic agent, the host reaction, and the
extent of involvement, determine the precise
form of pneumonia
Extremes of age, chronic diseases (congestive
heart failure, COPD, and diabetes), congenital or
acquired immune deficiencies, and decreased or
absent splenic function (sickle cell disease or
postsplenectomy, which puts the patient at risk
for infection with encapsulated bacteria such as
pneumococcus).

Streptococcus pneumoniae
Most common cause of community-acquired
acute pneumonia
Examination of gram-stained sputum
Presence of numerous neutrophils containing the
typical gram-positive, lancet-shaped diplococci
Isolation of pneumococci from blood cultures is
more specific but less sensitive
o In the early phase of illness, only 20% to
30% of patients have positive blood
cultures

Haemophilus Influenza
Pleomorphic, gram-negative organism that occurs
in encapsulated and nonencapsulated forms
Six serotypes of the encapsulated form (types a to
f), of which type b is the most virulent
Antibodies against the capsule protect the host
from H. influenzae infection; hence the capsular
polysaccharide b is incorporated in the widely

PATHOLOGY LUNGS (PULMONARY INFECTION AND TUMORS)

used vaccine against H. influenzae infections with
nonencapsulated forms, also called nontypeable
forms - are less virulent, spread along
The surface of the upper respiratory tract, and
produce otitis media (infection of the middle ear),
sinusitis, and bronchopneumonia.
o Neonates and children with comorbidities
such as prematurity, malignancy, and
immunodeficiency are at high risk for
development of invasive infection.
Descending laryngotracheobronchitis results in
airway obstruction as the smaller bronchi are
plugged by dense, fibrin-rich exudates containing
neutrophils
Pulmonary consolidation is usually lobular and
patchy but may be confluent and involve the
entire lung lobe
Common cause of suppurative meningitis in
children up to 5 years of age. H. influenzae also
causes an acute, purulent conjunctivitis (pink eye)
in children and, in predisposed older patients,
may
cause
septicemia,
endocarditis,
pyelonephritis, cholecystitis, and suppurative
arthritis
Most common bacterial cause of acute
exacerbation of COPD

Moraxella catarrhalis
Bacterial pneumonia, especially in the elderly
Second most common bacterial cause of acute
exacerbation of COPD
Constitutes one of the three most common causes
of otitis media in children

Staphylococcus aureus
Secondary bacterial pneumonia in children and
healthy adults following viral respiratory illnesses
(e.g., measles in children and influenza
High incidence of complications, such as lung
abscess and empyema
Intravenous drug users are at high risk for
development of staphylococcal pneumonia in
association with endocarditis
Important cause of hospital-acquired pneumonia

Klebsiella pneumoniae
Most frequent cause of gram- negative bacterial
pneumonia
Afflicts debilitated and malnourished people,
particularly chronic alcoholics

Thick, mucoid, (often blood-tinged) sputum

o Organism produces an abundant viscid
capsular polysaccharide, which the
patient may have difficulty expectorating

Pseudomonas aeruginosa
Most commonly causes hospital-acquired
infections
Cystic fibrosis and immunocompromised patients
Common in patients who are neutropenic and it
has a propensity to invade blood vessels with
consequent extrapulmonary spread
Pseudomonas septicemia is a very fulminant
disease

Legionella pneumophila
Agent of Legionnaires disease
Causes Pontiac fever - a related self-limited upper
respiratory tract infection
Mode of transmission is either inhalation of
aerosolized organisms or aspiration of
contaminated drinking water
Predisposing conditions such as cardiac, renal,
immunologic, or hematologic disease
Organ transplant recipients
Quite severe, frequently requiring hospitalization,
and immunosuppressed patients may have fatality
rates of up to 50%
Demonstration of Legionella antigens in the urine
or by a positive fluorescent antibody test on
sputum samples; culture remains the diagnostic
gold standard

Mycoplasma pneumoniae
Common among children and young adults
Occur sporadically or as local epidemics in closed
communities (schools, military camps, and
prisons)

Morphology
Two patterns of anatomic distribution: lobular
bronchopneumonia and lobar pneumonia
Bronchopneumonia patchy consolidation
Lobar pneumonia - consolidation of a large
portion of a lobe or of an entire lobe
Same organisms may produce either pattern
depending on patient susceptibility
Most important from the clinical standpoint are
identification of the causative agent and
determination of the extent of disease.

PATHOLOGY LUNGS (PULMONARY INFECTION AND TUMORS)

(1st photo): Bronchopneumonia. Section of lung
showing patches of consolidation (arrows)
(2nd photo): Lobar pneumoniagray hepatization.
The lower lobe is uniformly consolidated.

In lobar pneumonia, four stages of the
inflammatory response have classically been
described: congestion, red hepatization, gray
hepatization, and resolution
CONGESTION
o The lung is heavy, boggy, and red
o Characterized by vascular engorgement,
intra-alveolar fluid with few neutrophils,
and often the presence of numerous
bacteria
RED HEPATIZATION
o Massive confluent exudation, as
neutrophils, red cells, and fibrin fill the
alveolar spaces
o The lobe is red, firm, and airless, with a
liver-like consistency
GRAY HEPATIZATION
o Marked by progressive disintegration of
red cells and the persistence of a
fibrinosuppurative exudate
RESOLUTION

The exudate within the alveolar spaces is

broken down by enzymatic digestion to
produce granular, semifluid debris that is
resorbed, ingested by macrophages,
expectorated, or organized by fibroblasts
growing into it
o Pleural fibrinous reaction to the
underlying inflammation, often present in
the early stages if the consolidation
extends to the surface (pleuritis), may
similarly resolve
o Undergoes organization, leaving fibrous
thickening or permanent adhesions
Foci of bronchopneumonia are consolidated areas
of acute suppurative inflammation
o The consolidation may be confined to one
lobe
o More often multilobar and frequently
bilateral and basal because of the
tendency of secretions to gravitate to the
lower lobes
o elicits a neutrophil-rich exudate that fills
the bronchi, bronchioles, and adjacent
alveolar spaces
o

Stages of bacterial pneumonia.

A, Acute pneumonia. The congested septal
capillaries and numerous intra-alveolar
neutrophils are characteristic of early red
hepatization. Fibrin nets have not yet formed.
B, Early organization of intra-alveolar exudate,
seen focally to be streaming through the pores of
Kohn
C, Advanced organizing pneumonia. The exudates
have been converted to fibromyxoid masses rich in
macrophages and fibroblasts.

Complications of pneumonia include:

o (1) Tissue destruction and necrosis,
causing abscess formation (particularly
common with type 3 pneumococci or
Klebsiella infections)
o (2) Spread of infection to the pleural
cavity, causing the intra-pleural
fibrinosuppurative reaction known as
empyema
o (3) Bacteremic dissemination to the
heart valves, pericardium, brain, kidneys,
spleen, or joints, causing metastatic

PATHOLOGY LUNGS (PULMONARY INFECTION AND TUMORS)

abscesses, endocarditis, meningitis, or

suppurative arthritis.
Abrupt onset of high fever, shaking chills,
and cough producing mucopurulent
sputum occasional hemoptysis
Accompanied by pleuritic pain and pleural
friction rub

Severe Acute Respiratory Syndrome
Severe acute respiratory syndrome (SARS) first
appeared in November 2002 in the Guangdong
Province of China and subsequently spread to
Hong Kong, Taiwan, Singapore, Vietnam, and
Toronto,
Cause of SARS was a new coronavirus.

Health Care-Associated Pneumonia
Health-care associated pneumonia was recently
described as a distinct clinical entity associated
with significant risk factors.
o Hospitalization of at least 2 days within
the recent past
o Presentation from a nursing home or
long-term care facility
o Attending a hospital or hemodialysis clinic
o Recent intravenous antibiotic therapy,
chemotherapy or wound-care.
The most common organisms isolated are
methicillin-resistant Staphylococcus aureus and P.
aeruginosa. These patients have a higher mor-
tality than those with community-acquired
pneumonia.

Hospital Acquired Pneumonia
Hospital-acquired pneumonias are defined as
pulmonary infections acquired in the course of a
hospital stay.
o Severe underlying disease
o Immunosuppression
o Prolonged antibiotic therapy, or invasive
access devices such as intravascular
catheters
o Patients on mechanical ventilation are at
particularly high risk.
Superimposed on an underlying disease (that
caused
hospitalization),
hospital-acquired

Community-Acquired Viral Pneumonia

Influenza Infections
Influenza viruses of type A infect humans, pigs,
horses, and birds and are the major cause of
pandemic and epidemic influenza infections.

Human Metapneumovirus
Human metapneumovirus (MPV), a
paramyxovirus discovered in 2001, is found
worldwide and is associated with upper and lower
respiratory tract infections.
Human MPV can cause severe infections such as
bronchiolitis and pneumonia and is responsible

for 5% to 10% of hospitalizations and 12% to 20%

of outpatient visits of children suffering from
acute respiratory tract infections.
Diagnostic methods include PCR tests for viral
RNA and direct immunofluorescence.
Ribavirin is the only antiviral treatment that is
currently available for human MPV infections; it is
used mostly in immunocompromised patients
with severe disease.

PATHOLOGY LUNGS (PULMONARY INFECTION AND TUMORS)

otherwise
immunosuppressed
individuals are at special risk
a. Septic embolism: Infected
emboli
from
thrombophlebitis in any
portion of the systemic
venous circulation or from
the vegetations of infective
bacterial endocarditis on the
right side of the heart are
trapped in the lung
b. Neoplasia - (postobstructive
pneumonia)
c. Miscellaneous:
Direct
traumatic penetrations of
the lungs; spread of
infections
from
a
neighboring organ, such as
suppuration
in
the
esophagus, spine, subphrenic
space, or pleural cavity; and
hematogenous seeding of
the lung by pyogenic
organisms all may lead to
lung abscess formation
When all these causes are excluded, there are still
cases in which no reasonable basis for the abscess
formation can be identified. These are referred to
as primary cryptogenic lung abscesses

Morphology
Abscesses vary in diameter from lesions of a few
millimeters to large cavities of 5 to 6 cm.
Pulmonary abscesses due to aspiration are more
common on the right (because of the more
vertical right main bronchus) and are most often
single.
Abscesses that develop in the course of
pneumonia or bronchiectasis are usually multiple,
basal, and diffusely scattered. Septic emboli and
pyemic abscesses are multiple and may affect any
region of the lungs.
The cardinal histologic changes in all abscesses is
Suppurative destruction of the lung parenchyma
within the central area of cavitation
Superimposed saprophytic infections are prone to
develop within the already necrotic debris
Continued infection leads to large, fetid, greenblack, multilocular cavities with poor demarcation
of their margins, designated gangrene of the lung.

infections are serious and often life-threatening

complications.
Gram-positive cocci (mainly S. aureus and S.
pneumonia)
and
gram-negative
rods
(Enterobacteriaceae and Pseudomonas species)
are the most common isolates.

Aspiration Pneumonia
Aspiration pneumonia occurs in markedly
debilitated patients or those who aspirate gastric
contents either while unconscious (e.g., after a
stroke) or during repeated vomiting.
Typically, more than one organism is recovered on
culture, aerobes being more common than
anaerobes.
This type of pneumonia is often necrotizing,
pursues a fulminant clinical course, and is a
frequent cause of death.
Lung abscess is a common complication.

Lung Abscess
Local suppurative process within the lung,
characterized by necrosis of lung tissue
Oropharyngeal surgical procedures, sinobronchial
infections,dental sepsis, and bronchiectasis play
important roles in theirdevelopment

Etiology and Pathogenesis
Aerobic and anaerobic streptococci, S. aureus, and
a host of gram-negative organisms.
Anaerobic organisms normally found in the oral
cavity, including members of the Bacteroides,
Fusobacterium, and Peptococcus species
The causative organisms are introduced by the
following mechanisms:
o Aspiration of infective material (the most
frequent cause)
common in acute alcoholism,
coma, anesthesia, sinusitis,
gingivodental
sepsis,
and
debilitation in which the cough
reflexes are depressed
cause
pneumonia
which
progresses to tissue necrosis and
lung abscess
o Antecedent primary lung infection:
Post-pneumonic abscess formations
are usually associated with S. aureus,
K. pneumoniae, and the type 3
pneumococcus. Posttransplant or

PATHOLOGY LUNGS (PULMONARY INFECTION AND TUMORS)

Fibroblastic proliferation produces a fibrous wall

Clinical Course
Cough, fever, and copious amounts of foulsmelling purulent or sanguineous sputum
Fever, chest pain, and weight loss are common
Clubbing of the fingers and toes may appear
within a few weeks after the onset of an abscess
In older individuals, it is important to rule out an
underlying carcinoma, because this is present in
10% to 15% of cases
With antimicrobial therapy, most resolve leaving
behind a scar
Complications include extension of the infection
into the pleural cavity, hemorrhage, the
development of brain abscesses or meningitis
from septic emboli, and (rarely) secondary
amyloidosis (type AA)

Chronic Pneumonia
A localized lesion in the immunocompetent
patient, with or without regional lymph node
involvement

The inflammatory reaction is granulomatous, and
is caused by bacteria (e.g., M. tuberculosis) or
fungi (e.g., Histoplasma capsulatum)

Histoplasmosis
Acquired by inhalation of dust particles from soil
contaminated with bird or bat droppings that
contain small spores (microconidia)
H. capsulatum is an intracellular pathogen that is
found mainly in phagocytes

The clinical presentations and morphologic lesions

of histoplasmosis also strikingly resemble those of
tuberculosis, including
o Self-limited and often latent primary
pulmonary involvement, which may result
in coin lesions on chest radiograph
o Chronic, progressive, secondary lung
disease, which is localized to the lung
apices and causes cough, fever, and night
sweats
o Localized lesions in extrapulmonary sites,
including mediastinum, adrenals, liver, or
meninges
o A widely disseminated disease in
immunocompromised patients
Macrophages are the major target of infection.
Internalized into macrophages after opsonization
with antibody
Can multiply within the phagosome, and lyse the
host cells
Histoplasma induces macrophages to secrete TNF,
which recruits and stimulates other macrophages
to kill Histoplasma

Morphology
Histoplasma infections produce granulomas,
which usually undergo caseation necrosis and
coalesce to produce large areas of consolidation
but may also liquefy to form cavities
With spontaneous or drug control of the infection,
these lesions undergo fibrosis and concentric
calcifi cation (tree-bark appearance)
requires identification of the 3- to 5-m thinwalled yeast forms that may persist in tissues for
years
In fulminant disseminated histoplasmosis, which
occurs in immunosuppressed individuals,
epithelioid cell granulomas are not formed;
instead, there are focal accumulations of
mononuclear phagocytes filled with fungal yeasts
throughout the tissues and organs of the body

Diagnosis
The diagnosis of histoplasmosis is established by
culture or identification of the fungus in tissue
lesions
Serologic tests for antibodies and antigen are also
available.

PATHOLOGY LUNGS (PULMONARY INFECTION AND TUMORS)

Antigen detection in body fluids is most useful in
the early stages, because antibodies are formed 2
to 6 weeks after infection.

Blastomycosis
Blastomyces dermatitidis is a soil-inhabiting,
dimorphic fungus
There are three clinical forms: pulmonary
blastomycosis, disseminated blastomycosis, and a
rare primary cutaneous form that results from
direct inoculation of organisms into the skin
abrupt illness with productive cough, headache,
chest pain, weight loss, fever, abdominal pain,
night sweats, chills, and anorexia
Chest radiographs reveal lobar consolidation,
multilobar infi ltrates, perihilar infi ltrates,
multiple nodules, or miliary infltrates
The upper lobes are most frequently involved
Pneumonia most often resolve spontaneously, but
it may persist or progress to a chronic lesion

Morphology
In the normal host the lung lesions of
blastomycosis are suppurative granulomas
Macrophages have a limited ability to ingest and
kill B. dermatitidis, and the persistence of the
yeast cells leads to continued recruitment of
neutrophils.
In tissue, B. dermatitidis is a round, 5- to 15-um
yeast cell that divides by broad-based budding
o thick, double-contoured cell wall, and
visible nuclei
Involvement of the skin and larynx is associated
with marked epithelial hyperplasia

Coccidiomycosis
Develops a delayed-type hypersensitivity to the
fungus
Infective arthroconidia, when ingested by alveolar
macrophages, block fusion of the phagosome and
lysosome and so resist intracellular killing
Asymptomatic, but 10% of people have lung
lesions, fever, cough, and pleuritic pains,
accompanied by erythema nodosum or erythema
multiforme (the San Joaquin Valley fever complex)
Develop disseminated C. immitis infection, which
frequently involves the skin and meninges.

Morphology

Primary and secondary lung lesions of C. immitis

are similar to the granulomatous lesions of
Histoplasma
Within macrophages or giant cells, C. immitis is
present as thick-walled, nonbudding spherules 20
to 60 m in diameter, often filled with small
endospores
Pyogenic reaction is superimposed when the
spherules rupture to release the endospores
Rare progressive C. immitis disease involves the
lungs, meninges, skin, bones, adrenals, lymph
nodes, spleen, or liver
The inflammatory response may be purely
granulomatous, pyogenic, or mixed
Purulent lesions dominate in patients with
diminished resistance and with widespread
dissemination.

Pneumonia in the Immunocompromised Host
The appearance of a pulmonary infiltrate, with or
without signs of infection (e.g., fever), is one of
the most common and serious complications in
patients whose immune defenses are suppressed
by disease, immunosuppressive therapy for
organ transplants, chemotherapy for tumors, or
irradiation
A wide variety of so-called opportunistic
infectious agents, many of which rarely cause
infection in normal hosts, can cause these
pneumonias, and often more than one agent is
involved
Of these, the ones that commonly involve the lung
can be classifi ed according to the etiologic agent:
o Bacteria (P. aeruginosa, Mycobacterium
species, L. pneumophila, and Listeria
monocytogenes),
o Viruses (cytomegalovirus [CMV] and
herpesvirus)
o Fungi (P. jiroveci, Candida species,
Aspergillus species, the Phycomycetes,
and Cryptococcus neoformans)

Pulmonary Disease in Human Immunodeficiency Virus
Infection
Pulmonary disease accounts for 30%-40% of
hospitalization in HIV-infected individuals
The implicated organisms include S. pneumoniae,
S. aureus, H. influenzae, and gram-negative rods
Not all pulmonary infiltrates in HIV-infected
individuals are infectious in etiology
7

PATHOLOGY LUNGS (PULMONARY INFECTION AND TUMORS)

The CD4+ T-cell count can define the risk of

infection with specific organisms.

PULMONARY TUMORS
90% to 95%: carcinomas
5%: bronchial carcinoids
2% to 5%: are mesenchymal
Benign: management is surgery if the tumor is
resectable
Malignant: know the extent of tumor spread by
staging. Management depends on the stage. (ex.
Stage 4: Paliative)
Primary Tumor
Carcinomas: epithelial in origin; 90% of
the Lung Cancer
Sarcomas: mesenchymal in origin
Metastatic


most common cancer in the Lungs
*Most common primary cancer in the lungs:
Adenocarcinoma

Etiology and Pathogenesis
Cigarette/Tobacco Smoking
No. 1 risk factor.
80% of lung cancers occur in active smokers
or those who stopped recently
Measure the load of smoking by computing
for the pack years.
20 pack years or more (2 packs/day for 20
years) greatly increase the risk of lung cancer.
Women have a higher susceptibility to
carcinogens in tobacco than men
Second hand smoke, or environmental
tobacco smoke contains numerous human
carcinogens for which there is no safe level of
exposure
Industrial Hazards
e.g. Asbestos (formerly part of cement
mixture)
Certain industrial exposures such as arsenic,
chromium, uranium, nickel, vinyl chloride and
mustard gas
High-dose ionizing radiation
The latent period before the development of
lung cancer is 10 to 30 years
Air Pollution
Chronic exposure to air particulates in smog
may cause lung irritation, inflammation and
repair.

A specific form of air pollution that may

contribute to an increased risk of lung cancer
is radon gas.
Molecular genetics
Increase risk for lung cancer even among the
non-smokers
Smoking-related carcinomas of the lung arise
by a stepwise accumulation of oncogenic
driver mutations that result in the
neoplastic transformation of pulmonary
epithelial cells
Never Smokers
due to second hand smoke (Passive Smoking)
These cancers occur more commonly in
women and most are adenocarcinomas
EGFR mutations
Precursor Lesions
Antecedent events to the development of
lung carcinoma; predisposition to carcinoma
is more of genetics rather than
environmental.
Environmental factor may be an initiator but
the patient must be genetically predisposed.
Best time to detect before carcinoma
develops because it is still curable;
Practically it is difficult to detect: CXR cant
detect tumors smaller than 1 cm; CT scan is
relatively expensive. Tumor marker calcitonin
is not specific
Detection relies on clinical manifestations

Carcinomas

Squamous Dysplasia and Carcinoma in

Situ
May develop to Squamous cell
CA.
Atypical cells may be identified
in cytologic smears of sputum or
in bronchial lavage fluids or
brushings
Atypical Adenomatous Hyperplasia
May develop to adenocarcinoma
Small lesion (5 mm)
Dysplastic pneumocytes lining
alveolar walls that are mildly
fibrotic
Adenocarcinoma in situ
May develop to adenocarcinoma
Formerly
called
bronchioloalveolar carcinoma

PATHOLOGY LUNGS (PULMONARY INFECTION AND TUMORS)

Less than 3 cm
Composed entirely of dysplastic
cells growing along preexisting
alveolar septae
Cells have more dysplasia than
atypical
adenomatous
hyperplasia and may or may not
have intracellular mucin
Diffuse Idiopathic neuroendocrine cell
hyperplasia
may develop to small cell
carcinoma

Tumor Location
Central vs. Peripheral
Central Tumors
Not amenable to surgery as they are adjacent
to mediastinal structures
High possibility that it may be a small cell or a
squamous cell carcinoma
Biopsy is relatively easier to perform
May cause obstruction of the airways:
wheezing
They may completely block some of the
airways as manifested by absence of breath
sounds in that area.
Peripheral Tumors
Resectable
High possibility for adenocarcinoma
CT scan guided needle biopsy
Multiple Location
Maybe secondary tumors from metastasis

Diagnosis
Clinical exam:
Physical exam: Dull on percussion suggests a
mass. (Normal percussion of the lungs: resonance)
CXR: appears white on radiology
After detection of mass, the next important thing is to
determine whether it is benign or malignant (through
biopsy). If it is malignant classify it according to:

Adenocarcinoma
Invasive malignant epithelial tumor with
glandular differentiation or mucin production
by the tumor cells.
Grow in various patterns, including acinar,
lepidic, papillary, micropapillary, and solid
with mucin formation.

Lesions are usually more peripherally located

and tend to be smaller
Microinvasive Adenocarcinoma: Tumors (3
cm) with a small invasive component (5 mm)
associated with scarring and a peripheral
lepidic growth pattern.
Mucinous
Adenocarcinomas:
spread
aerogenously, forming satellite tumors.
Present as a solitary nodule or as multiple
nodules, or an entire lobe may be
consolidated by tumor, resembling lobar
pneumonia
Squamous Cell carcinoma
Most commonly found in men and is strongly
associated with smoking
Characterized by the presence of
keratinization (squamous pearls or individual
cells with markedly eosinophilic dense
cytoplasm) and/or intercellular bridges.
Small Cell Carcinoma
Highly malignant tumor with the strongest
relationship to cigarette smoking (only 1%
are non-smokers)
Most aggressive of lung tumors, metastasizing
widely comprised of relatively small cells with
scant cytoplasm, ill-defined cell borders, finely
granular nuclear chromatin (salt and pepper
pattern), and absent or inconspicuous
nucleoli.
Cells are round, oval, or spindleshaped, and
nuclear molding is prominent - cells are small
(3x smaller than lymphocytes)
Large Cell Carcinoma
Undifferentiated malignant epithelial tumor
that lacks the cytologic features of other
forms of lung cancer.
Cells typically have large nuclei, prominent
nucleoli, and a moderate amount of
cytoplasm
Diagnosis of exclusion since it expresses none
of
the
markers
associated
with
adenocarcinoma and squamous cell
carcinoma

Complications
Partial obstruction may cause marked focal
emphysema.
Total obstruction may lead to atelectasis
Impaired drainage of the airways is a common
cause for severe suppurative or ulcerative
9

PATHOLOGY LUNGS (PULMONARY INFECTION AND TUMORS)

bronchitis or bronchiectasis
Compression or invasion of the superior vena cava
can cause venous congestion and edema of the
head and arm, and, ultimately, circulatory
compromisethe superior vena cava syndrome
Extension to the pericardial or pleural sacs may
cause pericarditis or pleuritis with significant
effusions.

In detecting tumors of the lungs:
1. Determine whether it is located in the central
or peripheral
2. Determine if it is benign or malignant
3. If it is malignant, determine the staging.
4. From staging, determine the treatment:
surgery, radiotherapy, chemotherapy or
combination.

Genetics majority unknown
Genes:
*Adenocarcinoma KRAS (#1), EGFR
*Squamous FGFR (#1), PIK3 CA, KRAS
*HER2 originally for breast cancer detection, now it is
found out that it can also be detected in gastric and lung
cancer

Clinical Manifestation
In the usual case it is discovered in patients in
their 50s or older whose symptoms are of several
months duration (Late detection)
Early stages: no symptoms; so it is very difficult to
detect early because patients will not seek
consultation (asymptomatic).
Symptoms may appear when the cancer has
advanced. There may be bleeding, obstruction
and spread of the tumor cells.
When patient seeks consultation, the cancer may
already be in the late stages.
Once the patient seeks consultation, perform
history taking (about exposure to risk factors),
physical examination, chest x-ray (detect mass
and its location), biopsy (detect type of
malignancy)
Cough: most common; usually dry, nonproductive
Hemoptysis: second most common manifestation
Chest pain: if its just confined within the lung,

there is no pain felt. Pain is produce when tumor

invades the pain-sensitive areas like the
mediastinum, pleura, chest wall, ribs or even the
adjacent muscles. Chest pain may suggest that the
cancer is far-advanced.
Symptoms of metastases depend on the site, for
example, back pain in bone metastases,
headache, hemiparesis, cranial nerve damage, and
seizures in brain metastases.

Neuroendocrine Tumors
Rare
Carcinoid; proliferation of neuroendocrine cells.
Septa is still intact but the spaces are filled with
neuroendocrine cells (see picture below)
Still benign but can become malignant in the form
of small cell carcinoma
Common in the periphery (resectable)
Since it is a neuroendocrine tumor, it may
elaborate hormones giving rise to Paraneoplastic
syndrome.

Paraneoplastic Syndrome
- Manifestations depend on the
hormone
released
(endocrinopathies); examples:
Antidiuretic Hormone (ADH):
Responsible for water reabsorption.
Manifestation includes fluid overload (edema
and CHF) due to water reabsorption (decrease
urination)
hyponatremia
Predominantly small cell CA
Adrenocorticotropic Hormone (ACTH)
Production of cortisol. Manifestations are
based on the effects of cortisol.
Cushings syndrome
Predominantly small cell CA
Parathormone, parathyroid hormone-related
peptide, prostaglandin E, and some cytokines
hypercalcemia
Mostly squamous cell CA
Calcitonin
hypocalcemia
Gonadotropins
gynecomastia
Serotonin and bradykinin
Carcinoid syndrome (intermittent attacks of
diarrhea, flushing, and cyanosis)
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PATHOLOGY LUNGS (PULMONARY INFECTION AND TUMORS)

Other systemic manifestation of Lung Cancer:
Lambert-Eaton myasthenic syndrome
Muscle weakness caused by auto-antibodies
(possibly elicited by tumor ionic channels)
directed to the neuronal calcium channel.
Peripheral neuropathy
Usually purely sensory
Acanthosis nigricans
Leukemoid reactions
Hypercoagulable states such as Trousseau syndrome
Deep vein thrombosis and thromboembolism
Hypertrophic pulmonary osteoarthropathy
Associated with clubbing of the fingers

Carcinoid Tumors
Most patients with these tumors are younger than
40 years of age, and the incidence is equal for
both sexes
Low-grade malignant epithelial neoplasms that
are
subclassified
into
typical
and
atypicalcarcinoids.
Carcinoids may arise centrally or may be
peripheral.
Central tumors grow as fingerlike or spherical
polypoid masses that commonly project into the
lumen of the bronchus and are usually covered by
an intact mucosa
Most are confined to the mainstem bronchi.
Others, penetrate the bronchial wall to fan out in
the peribronchial tissue, producing collar-button
lesion
Tumor is composed of organoid, trabecular,
palisading, ribbon, or rosette-like arrangements of
cells separated by a delicate fibrovascular stroma
Functioning lesions capable of producing the
classic carcinoid syndrome, characterized by
intermittent attacks of diarrhea, flushing, and
cyanosis.

Miscellaneous Tumors
Lung hamartoma
is a relatively common lesion that is usually
discovered as an incidental, rounded radio-opacity
(coin lesion) on a routine chest film
Solitary, less than 3 to 4 cm in diameter, and well
circumscribed
Consists 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.
Lymphangioleiomyomatosis
Primarily affects young woman of childbearing age
Proliferation of perivascular epithelioid cells that
express markers of both melanocytes and smooth
muscle cells.
Proliferation distorts the involved lung, leading to
cystic, emphysema-like dilation of terminal
airspaces, thickening of the interstitium, and
obstruction of lymphatic vessels.
Inflammatory myofibroblastic tumor
Rare; more common in children
Presenting symptoms include fever, cough, chest
pain, and hemoptysis.
Imaging studies show a single (rarely multiple)
round, well-defined, usually peripheral mass with
calcium deposits in about a quarter of cases.
Lesion is firm, 3 to 10 cm in diameter, and grayish
white
there is proliferation of spindle-shaped fibroblasts
and myofibroblasts, lymphocytes, plasma cells,
and peripheral fibrosis

Metastatic Tumors
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.
Metastatic tumors: multiple masses
Multiple discrete nodules (cannonball lesions) are
scattered throughout all lobes, more being at the
periphery
Secondary Lung Cancer
Primary responsibility is to determine where the
primary tumor is
Histologic type depends on the organ of origin
No surgery done

MEDIASTINAL TUMORS
Central mass
Located on central thoracic region
Part of differential diagnosis for centrally located

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PATHOLOGY LUNGS (PULMONARY INFECTION AND TUMORS)

tumors (not all central tumors are

small/squamous cell lung CA, others are
mediastinal tumors)
Subdivided into: anterior, middle or posterior.
Diagnosis: Lateral X-ray; It determines whether
the tumor is really mediastinal or just a centrally
located lung tumor.
Determine the radiodensity. If it is behind the
trachea and primary bronchus, most likely it is a
mediastinal tumor.

Most common causes of pleuritic are disorders

associated with inflammation of the underlying
lung
Systemic disorders, and metastatic involvement of
the pleura can also cause serous or serofibrinous
pleuritis.
Radiation used in therapy for tumors in the lung
or mediastinum often causes a serofibrinous
pleuritic
Purulent pleural exudate (empyema) usually
results from bacterial or mycotic seeding of the
pleural space.
Empyema is characterized by loculated, yellowgreen, creamy pus composed of masses of
neutrophils admixed with other leukocytes
Hemorrhagic pleuritis manifested by sanguineous
inflammatory exudates is infrequent and is found
in hemorrhagic diatheses, rickettsial diseases, and
neoplastic involvement of the pleural cavity.
Noninflammatory Pleural Effusions
Noninflammatory collections of serous fluid within
the pleural cavities are called hydrothorax
Fluid is clear and straw colored
The most common cause of hydrothorax is
cardiac failure, and for this reason it is usually
accompanied by pulmonary congestion and
edema.
The escape of blood into the pleural cavity is
known as hemothorax. It is almost invariably a
fatal complication of a ruptured aortic aneurysm
or vascular trauma or it may occur
postoperatively.
Chylothorax is an accumulation of milky fluid,
usually of lymphatic origin, in the pleural cavity.
Chyle is milky white because it contains finely
emulsified fats.
Chylothorax is most often caused by thoracic
duct trauma or obstruction that secondarily
causes rupture of major lymphatic ducts
Disorder is typically caused by malignancies that
obstruct the major lymphatic ducts.

Pneumothorax
Air accumulation in the pleural cavity
Usually associated with paracentral or distal
emphysema (COPD). Bulla may rupture and cause
air leakage
Most commonly associated with emphysema,
asthma, and tuberculosis

DISEASES OF THE PLEURA
Most of the time, they are secondary
complication of an underlying disease
Primary disorders include: (1) primary intrapleural
bacterial infections that imply seeding of this
space as an isolated focus in the course of a
transient bacteremia and (2) a primary neoplasm
of the pleura: mesothelioma

Pleural Effusion:
Fluid accumulation
Normally, no more than 15 mL of serous,
relatively acellular, clear fluid lubricates the
pleural surface
Determine whether it is inflammatory (exudates:
rich in WBCs and proteins) or non-inflammatory
(transudates).
Non-inflammatory cause involves fluid imbalance
(disturbance in the Frank Starling forces).
Examples: Cardiac failure: increase intravascular
hydrostatic
pressure.
Hypoalbuminemia:
Decrease intravascular oncotic pressure.

Accumulation of pleural fluid occurs in the following
settings:
Increased hydrostatic pressure, as in congestive
heart failure
Increased vascular permeability, as in pneumonia
Decreased osmotic pressure, as in nephrotic
syndrome
Increased intrapleural negative pressure, as in
atelectasis
Decreased lymphatic drainage, as in mediastinal
carcinomatosis

Inflammatory Pleural Effusions

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PATHOLOGY LUNGS (PULMONARY INFECTION AND TUMORS)

It may be spontaneous, traumatic, or therapeutic.

Spontaneous pneumothorax may complicate
any form of pulmonary disease that causes
rupture of an alveolus.
Traumatic pneumothorax is usually caused by
some perforating injury to the chest wall but
sometimes the trauma pierces the lung and
thus provides two avenues for the
accumulation of air within the pleural spaces.
Spontaneous idiopathic pneumothorax is due
to rupture of small, peripheral, usually apical
subpleural blebs, and usually subsides
spontaneously as the air is resorbed.

Tumors of the Pleura
Most common pleural cancer is metastatic
The most frequent metastatic malignancies arise
from primary neoplasms of the lung and breast.
Most common primary tumor: mesothelioma
Benign
Fibrous tumor, histology reveals fibrous
collagen
Solitary Fibrous Tumor
Consists of dense fibrous tissue with
occasional cysts filled with viscid fluid
Microscopically, the tumor shows whorls of
reticulin and collagen fibers among which are
interspersed spindle cells resembling
fibroblasts
Malignant Mesothelioma
Encases the lungs; rare but common on
environmental/occupational exposures (asbestos)
Increased incidence among people with heavy
exposure to asbestos
Asbestos bodies are found in increased numbers
in the lungs of patients with mesothelioma
The presenting complaints are chest pain,
dyspnea, and, as noted, recurrent pleural
effusions.
The lung is invaded directly, and there is often
metastatic spread to the hilar lymph nodes and,
eventually, to the liver and other distant organs
Malignant mesothelioma is a diffuse lesion arising
either from the visceral or parietal pleura, that
spreads widely in the pleural space and is usually
associated with extensive pleural effusion and
direct invasion of thoracic structures
Affected lung becomes ensheathed by a thick
layer of soft, gelatinous, grayish pink tumor tissue.

13

Microscopically, malignant mesotheliomas may be

epithelioid (60%), sarcomatoid (20%), or mixed
(20%).
Epithelioid type of mesothelioma consists of
cuboidal, columnar, or flattened cells forming
tubular or papillary structures resembling
adenocarcinoma.
The mesenchymal type of mesothelioma
(sarcomatoid type) appears as a spindle cell
sarcoma, resembling fibrosarcoma.
Mixed (biphasic) type of mesothelioma
Contains
both
epithelioid
and
sarcomatoid patterns
- Mesotheliomas also arise in the peritoneum,
pericardium, tunica vaginalis, and genital tract
(benign adenomatoid tumor)



Bakit hindi nagmamahal ang fishball?
Kasi takot na siyang masaktan.
-Anonymous