Lung pathology

Lung pathology
Dr. Emile Musoni
SoM-CMHS

Objective
1.Identification of main
inflammatory disease and
neoplasm of the lung

Contents:
 Atelectasis
 Obstructive (lung airway) disease
 Pulmonary infections
 Lung tumors
 Pleural lesions
Dr. Emile Musoni , SMP/CMHS/UR 3

Atelectasis
 Atelectasis, also known as collapse, is
loss of lung volume caused by inadequate
expansion of air spaces. It results in
shunting of inadequately oxygenated
blood from pulmonary arteries into veins,
thus giving rise to a ventilation perfusion
imbalance and hypoxia.

 atelectasis is classified into three forms:
 Resorption atelectasis
 Compression atelectasis.
 Contraction atelectasis.

Dr. Emile Musoni , SMP/CMHS/UR 65/30/2016
Resorption atelectasis.
Resorption atelectasis occurs when an obstruction prevents air from
reaching distal airways.
The air already present gradually becomes absorbed,
and alveolar collapse follows.
Depending on the level of airway obstruction, an entire lung, a complete
lobe, or one or more segments may be involved. The most common cause
of resorption collapse is obstruction of a
bronchus by a mucous or mucopurulent plug.
This frequently occurs postoperatively but also may complicate
bronchial asthma, bronchiectasis, chronic bronchitis, tumor, or foreign body
aspiration, particularly in children.

Compression atelectasis.
Compression atelectasis (sometimes called passive or relaxation
atelectasis) is usually associated with accumulation of fluid, blood, or air
within the pleural cavity, which mechanically collapses the adjacent lung.
This is a frequent occurrence with pleural effusion, caused most
commonly by congestive heart failure (CHF). Leakage of air into the
pleural cavity (pneumothorax) also leads to compression atelectasis.
Basal atelectasis resulting from the elevated position of the diaphragm
commonly occurs in bedridden patients,
in patients with ascites, and during and after surgery.

Contraction atelectasis.
Contraction (or cicatrization) atelectasis occurs when either local or
generalized fibrotic changes in the lung or pleura hamper expansion and
increase elastic recoil during expiration.
Atelectasis (except when caused by contraction) is potentially
reversible and should be treated promptly to prevent
hypoxemia and superimposed infection of the collapsed
lung.

Obstructive lung (air ways)
 In their prototypical forms, the four
disorders in this group—emphysema,
chronic bronchitis, asthma, and
bronchiectasis—have distinct clinical and
anatomic characteristics but overlaps
between emphysema, bronchitis, and
asthma are common.

Emphysema
 Emphysema is characterized by abnormal
permanent enlargement of the air spaces
distal to the terminal bronchioles,
accompanied by destruction of their walls
without significant fibrosis.

Types of Emphysema
Emphysema is classified according to its anatomic distribution
within the lobule; as described earlier, the acinus is the
structure distal to terminal bronchioles, and a cluster of
three to five acini is called a lobule .
There are
four major types of emphysema:
(1) centriacinar, (2) panacinar,
(3) distal acinar, and
(4) irregular.
Only the first two
types cause clinically significant airway obstruction, with
centriacinar emphysema being about 20 times more
common than panacinar disease

Chronic Bronchitis
Chronic bronchitis is common among cigarette smokers and urban dwellers in
smog-ridden cities; some studies indicate that 20% to 25% of men in the 40- to
65-year-old age group have the disease.
The diagnosis of chronic bronchitis is made on clinical grounds: it is defined by
the presence of a persistent productive cough for at least 3 consecutive months
in at least 2 consecutive years. In early stages of the disease, the productive
cough raises mucoid sputum, but airflow is not obstructed. Some patients with
chronic.
bronchitis may demonstrate hyperresponsive airways with intermittent
bronchospasm and wheezing. A subset of bronchitic patients, especially heavy
smokers, develop chronic outflow obstruction, usually with associated
emphysema.

Asthmais a chronic inflammatory disorder of the airways
that causes recurrent episodes of wheezing, breathlessness,
chest tightness, and cough, particularly at night and/or
early in the morning.
The hallmarks of the disease are:
intermittent and reversible airway obstruction, chronic bronchial
inflammation with eosinophils,
bronchial smooth muscle cell hypertrophy and hyperreactivity, and increased
mucus secretion.
Some of the stimuli that trigger attacks in patients would
have little or no effect in persons with normal airways.
Many cells play a role in the inflammatory response, in
particular eosinophils, mast cells, macrophages, lymphocytes,
neutrophils, and epithelial cells.

Bronchiectasis
is the permanent dilation of bronchi and
bronchioles caused by destruction of the muscle and the
supporting elastic tissue, resulting from or associated withchronic
necrotizing infections.
It is not a primary disease but rather secondary to persisting infection
or obstruction caused by a variety of conditions. Once developed, it
gives rise to a characteristic symptom complex dominated by
cough and expectoration of copious amounts of purulent
sputum.
Diagnosis depends on an appropriate history
along with radiographic demonstration of bronchial dilation.

The conditions that most commonly predispose to
bronchiectasis include:
• Bronchial obstruction. Common causes are tumors, foreign
bodies, and occasionally impaction of mucus.
Congenital or hereditary conditions—for example:
In cystic fibrosis, widespread severe bronchiectasis results from obstruction
caused by the secretion of abnormally viscid mucus thus predisposing to
infections of the bronchial tree.
In immunodeficiency states, particularly immunoglobulin
deficiencies,
Necrotizing, or suppurative, pneumonia, particularly with
virulent organisms such as Staphylococcus aureus or
Klebsiella spp.,

Silicosis
Silicosis is currently the most prevalent chronic occupational
disease in the world. It is caused by inhalation of crystalline
silica, mostly in occupational settings. Workers in several
occupations but especially those involved in sandblasting
and hard-rock mining are at particular risk.
Clinical Features:
Silicosis usually is detected on routine chest radiographs
obtained in asymptomatic workers. The radiographs typically show a fine
nodularity in the upper zones of the lung, but pulmonary function is either
normal or only moderately affected.
The disease is slow to kill, but impaired pulmonary function may severely limit
activity. Silicosis is associated with an increased susceptibility to tuberculosis.
Nodules of silicotuberculosis often contain a central zone of caseation.

Asbestosis and Asbestos-Related Diseases
Asbestos is a family of crystalline hydrated silicates with a fibrous geometry.
On the basis of epidemiologic studies, occupational exposure to asbestos is
linked to (1) parenchymal interstitial fibrosis (asbestosis);
(2) localized fibrous
plaques or, rarely, diffuse fibrosis in the pleura;
(3) pleural
effusions;
(4) lung carcinomas;
(5) malignant pleural
and peritoneal mesotheliomas; and (6) laryngeal carcinoma.
An increased incidence of asbestos-related cancers in family members of
asbestos workers has alerted the general public to the potential hazards of
asbestos in the environment.

Clinical Features
The clinical findings in asbestosis are indistinguishable from those of
any other chronic interstitial lung disease.
Typically, progressively worsening dyspnea appears 10 to 20 years
after exposure. The dyspnea is usually accompanied by a cough
associated with production of sputum.
The disease may remain static or progress to congestive heart failure,
cor pulmonale, and death. Pleural plaques are usually asymptomatic
and are detected on radiographs as
circumscribed densities.

Inflammation
Superficial, interstitial, specific and granulomatous
 A. Superficial
bronchopneumonia: catarrhal, necrotizing, eosinophilic
 B. Interstitial
lung abscess:
interstitial pneumonia:
viral
mycoplasma
ricketts
fungi
pneumocystis
Idiopathic
desquamative pneumonitis

 C. Specific
Tbc
syphilis: pneumonia alba
D. Granulomatous lung processes
allergic bronchioalveolitis,
sarcoidosis:

Lung Tumors
 Lungs are frequently the site of
metastases.
 Primary lung cancer is a common disease.
 95% of primary lung tumors arise from the
bronchial epithelium.
 5% are miscellaneous group.
 The most common benign lesions are
hamartomas.

Bronchogenic carcinoma
 The number one cause of cancer-related deaths in
industrialized countries.
 Occurs between ages 40 and 70 years.

Etiology of bronchogenic carcinoma
1. Tobacco smoking:
 Positive relationship between tobacco smoking and lung cancer.
 Statistical association between the frequency of lung cancer and:
1. Amount of daily smoking.
2. Tendency to inhale.
3. The duration of smoking habit.
 Increased risk becomes 20 times greater among habitual heavy
smokers.
 Cessation of cigarette smoking for at least 15 years brings the
risk down.
 Passive smoking increases the risk to approximately twice than
non-smokers.
 Progressive alterations in the lining epithelium.
 Experimental evidence – more than 1200 carcinogenic and
promoter substances.

Etiology of brochogenic carcinoma
2. Industrial hazards:
 Certain industrial exposures increase the risk of
developing lung cancer.
 All types of radiation may be carcinogenic.
 Uranium miners (4x)
Uranium miners and smoking (10x).
 Asbestos worker (5x).
Asbestos worker and smoking (50-90x).
 Others: persons who work in nickel, chromates, coal,
mustard gas, arsenic, iron and in newspaper workers.

Etiology of bronchogenic carcinoma
3. Air pollution:
 May play some role in increased
incidence.
 Indoor air pollution especially by radon.
4. Scarring:
 Due to old infarcts, wounds, scar,
granulomatous infections are
associated with adenocarcinoma.

Precursor Lesions.
 Three types of precursor epithelial lesions
are recognized:
(1) squamous dysplasia and carcinoma in situ
(2) atypical adenomatous hyperplasia
(3) diffuse idiopathic pulmonary neuroendocrine
cell hyperplasia.
It should be noted that the term "precursor"
does not imply that progression to invasion will
occur in all cases.

Classification of brochogenic carcinoma
Histologic classification of bronchogenic carcinoma and
approximate incidence:
1. Squamous cell (epithelium) carcinoma (25%-40%)
2. Adenocarcinoma, including bronchioloalveolar
carcinoma
(25%-40%).
3. Large cell carcinoma (10%-15%).
4. Small cell lung carcinoma (SCLC) (20%-25%).
5. Combine patterns (5%-10%).
- Most frequent patterns:
- Mixed squamous cell ca
and adenocarcinoma.
- Mixed squamous cell ca
and SCLC.

Classification of brochogenic
carcinoma
 For therapeutic purposes,
bronchogenic carcinoma are classified
into:
1. Non- Small cell lung carcinoma (NSCLC)
2. Small cell lung carcinoma (SCLC)
(includes squamous cell, adenocarcinomas,
and large-cell carcinomas).

carcinoma
Non- Small cell lung ca:
Abundant cytoplasm; pleomorphic
nuclei with coarse chromatin
pattern; nucleoli often
prominent; glandular or
squamous architecture
Small cell lung carcinoma:
Scant cytoplasm; small,
hyperchromatic nuclei with
fine chromatin pattern;
nucleoli indistinct; diffuse
sheets of cells
Differences between SCLC and NSCLC:
Histology

Differences between SCLC and
NSCLC:
Markers
Small cell lung carcinoma
 Neuroendocrine
Markers
 Usually present
(dense core granules on
electron microscopy;
expression of
chromogranin, neuron-
specific enolase and
synaptophysin)
 Epithelial Markers:
 Usually absent
 Mucin: Absent
non Small cell lung
carcinoma
 Usually absent
• Usually present
 Present in adenoarcinoma

carcinoma
Parathyroid hormone-related
peptide (PTH-rp) in
squamous cell carcinoma
Adrenocorticotropic hormone,
antidiuretic hormone,
gastrin-releasing peptide,
calcitonin
Peptide Hormone Production

carcinoma
MYC family overexpression occur in both
• p16/CDKN2A is
commonly inactivated
• K-RAS oncogene
mutation occur in
adenocarcinoma
• high frequency of TP53
and RB gene mutation
• deletion of the short arm of
chromosome 3
Genetic differences between SCLC and NSCLC:

carcinoma
 >80%
 ∼20%
 >50%
 >50%
 ∼30% adenocarcinomas
 ∼20% (adenocarcinomas,
nonsmokers, women)
Tumor Suppressor Gene:
3p deletions >90%
RB mutations ∼90%
p16/CDKN2A ∼10%
p53 mutations >90%
Dominant Oncogene
Abnormalities:
KRAS mutations Rare
EGFR mutations Absent
Genetic differences between SCLC and NSCLC:

carcinoma
• Uncommonly complete
response
• NSCLCs are curable by
surgery (if limited to the
lung).
• Often complete response
to but recur invariably
Response to Chemotherapy and Radiotherapy

 Among the major histologic subtypes of
lung cancer, squamous and small-cell
carcinomas show the strongest
association with tobacco exposure.

Morphology of bronchogenic
carcinoma
 Arise in the lining epithelium of major bronchi.
 All are aggressive.
 All varieties have the capacity to synthesize bioactive
products.
 Small mucosal lesions, firm and gray-white, form
intraluminal masses, invade into adjacent lung
parenchyma, central necrosis, areas of hemorrhage,
extend to the pleura, invade the pleural activity.
 Spread to trachial and mediastinal lymph nodes.

Morphology of bronchogenic carcinoma
Spread of bronchogenic carcinoma
1. Lymphatic spread.
* successive chains of nodes (scalene nodes).
* involvement of the supraclavicular node
(Virchow’s node).
2. Extend into the pericardial or pleural spaces. Infiltrate the
superior vena cava. May invade the brachial or cervical
sympathetic plexus (Homer’s Syndrome).
3. Distant metastasis to liver (30-50%), adrenals (>50%),
brain (20%) and bone (20%).

Squamous cell carcinoma(SCC)
 More common in men and closely correlated with smoking.
 Arise centrally in major bronchi.
 Preceded
for years
by atypical
metaplasia
or dysplasia

Squamous cell carcinoma
(SCC)
 Histologically, these tumors
range from well-differentiated
squamous cell neoplasm to
poorly differentiated neoplasm.

Adenocarcinomas
Two forms:
1. Bronchial – derived carcinoma.
 Most common in patients under the age of 40,
women and non-smokers.
 May occur as central lesions but are usually more
peripherally, many arising in relation to peripheral
lung scars.
 Tend to metastasize widely at an early stage.
2. Bronchioloalveolar carcinoma
 Involve peripheral parts as a single nodule or more
often as multiple diffuse nodules.

Bronchial – derived
adenocarcinoma
– Histologically, they assume
a variety of forms, including
typical adenocarcinoma with
mucus secretion and
papillary or
bronchioloalveolar patterns.
Bronchioloalveolar carcinoma
Malignant cells spread along alveolar
wall

Small cell carcinomas (oat cell carcinoma)
 Highly malignant tumor, rarely resectable.
 More common in men.
 Strongly associated with cigarette smoking.
 Appear as pale gray, centrally located masses with
extension into the lung parenchyma.
 Early involvement of the hilar and mediastinal
nodes.

Small cell carcinomas (oat cell
carcinoma)
 Composed of small, dark, round
to oval, lymphocyte-like cells.
 Derived from neuroendocrine
cells of the lung.
 EM dense-core neurosecretory
granules.
 Ability to secrete a host of
polypeptide hormones (ACTH),
calcitonin, gastrin-releasing
peptide and chromogranin.

Large cell carcinoma
 Anaplastic carcinoma with
large cells probably
represent SCC or
adenocarcinoma.
 Poor prognosis.

Secondary pathology
 Partial obstruction – emphysema.
 Total obstruction – atelectasis and
chronic bronchitis.
 Pulmonary abscess.
 Pleuritis.

Clinical features of bronchogenic carcinoma

Clinical features of bronchogenic
carcinoma
 Apical neoplasms may invade the brachial or cervical
sympathetic plexus to cause severe pain in the
distribution of the ulnar nerve
or
to produce Horner syndrome (ipsilateral
enophthalmos, ptosis, miosis, and anhidrosis).
 Such apical neoplasms are sometimes called
Pancoast tumors, and the combination of clinical
findings is known as Pancoast syndrome.
 Pancoast tumor is often accompanied by destruction
of the first and second ribs and sometimes thoracic
vertebrae.

Clinical course of bronchogenic
carcinoma
 Silent, insidious lesions, chronic cough
and expectoration.
 Hoarseness, chest pain, superior vena
cava syndrome, pericardial or pleural
effusion.
 Symptoms due to metastatic spread.
 NSCLC have a better prognosis than
SCLC.
 Outlook is poor for most patients.

Paraneoplastic syndrome
3% to 10% develop overt paraneoplastic
syndromes.
 Neuromuscular syndromes.
 Clubbing of the fingers.
 Hematologic manifestations.
 Endocrine

Paraneoplastic syndrome
 Antidiuretic hormone (ADH), inducing hyponatremia owing to
inappropriate ADH secretion
 Adrenocorticotropic hormone (ACTH), producing Cushing syndrome
 Parathormone, parathyroid hormone-related peptide,
prostaglandin E, and some cytokines, all implicated in the
hypercalcemia often seen with lung cancer
 Calcitonin, causing hypocalcemia
 Gonadotropins, causing gynecomastia
 Serotonin and bradykinin, associated with the carcinoid syndrome
Hypercalcemia is most often encountered with squamous cell neoplasms, the
hematologic syndromes with adenocarcinomas. The remaining syndromes are
much more common with small-cell neoplasms,

Neuroendocrine tumors
Bronchial carcinoid
 Tumor with neuroendocrine differentiation arising from
Kulchitsky cells in the bronchial mucosa.
 Appear at an early age (mean 40 years) with equal sex
incidence.
 1-5% of all pulmonary neoplasms.
 Often resectable and curable.
 No relation with cigarette smoking or other
environmental factor.
 Carcinoid syndrome ( intermittent attacks of diarrhea,
flushing, and cyanosis)

Morphology of Neuroendocrine tumors
 Originate in mainstem bronchi.
 Two patterns:
- an obstructing polypoid, spherical
intraluminal mass;
- a mucosal plaque penetrating the
bronchial wall.
 Composed of uniform cuboidal cells that have regular round
nuclei with few mitoses and little or no anaplasia.

 serous pleuritis: frequent, good prognosis
 fibrinous pleuritis: more fibrin in exsudate –
fibrous adhesions
 haemorrhagic pleuritis: TBC, bleeding,
metastases
 purulent pleuritis: empyema
 caseous pleuritis: TBC
Pathology of pleura
Inflammation – pleuritis
Associated with inflammation of lungs (pneumonia,
abscesses, septic infarct), mediastinum. Non-
inflammatory pericarditis (fibrinous) associated with
pulmonary infarct.

Tumors
 mesothelioma: malignant epithelial, malignant sarcomatoid,
maligní epithelial – lymphohistiocytic variant, malignant
biphasic, well differentiated papillary, multicystic
 adenomatoid tumor: benign
 solitary fibrous tumor: usually benign, rarely malignant,
CD34+, Bcl-2+
 epitheloid haemangioendothelioma: CD31+, CD34+, FVIII+
 myofibroblastic inflammatory tumor of pleura: rare
 secondary: metastatic
Pathology of pleura

Exercises - Lung pathology
 Write the defintion of the following :
 Atelectasis
 Empyema
 Emphysema
 Bronchiectasis
 Write the Clinical features of asthma and
silicosis
 Write briefly on lung and pleura tumors.

References
 Kumar , Abbas, Fausto ,Aster, Robbins
basic pathology ,9th Ed.
 Rosai & Ackerman ,Surgical
Pathology,10th Ed.

Break
In the next session: Hepatobiliary system and
Pancreas pathology

Lung pathology

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