ZHANG WEI (张伟)

Associate Professor, Ph.D.

Institute of Pathology & Forensic Medicine

Department of Pathology & Patho-physiology

Zhejiang University School of Medicine

zwei72@zju.edu.cn

8-year system Curriculum

6nd Week Theme

Respiratory Diseases

Diseases

Chronic obstructive pulmonary disease, COPD

Chronic bronchitis

Pulmonary emphysema

Bronchiectasis

Bronchial asthma

Pneumoconiosis:Silicosis

Chronic cor pulmonale

Pulmonary infections: Pneumonia

Lobar pneumonia

Lobular pneumonia

Interstitial pneumonia

Pulmonary tuberculosis

Tumors of lung

Broadly defined：any infection in the lung.

Pathologically Defined: any inflammation of lung due to infection

affecting distal airways, especially alveoli, with the formation of an

inflammatory exudate.

Pneumonia

1. Etiological classification:

bacterial pneumonia

viral pneumonia

fungal pneumonia

mycoplasma pneumonia etc.

Classification of pneumonia

2. Anatomical classification:

lobar pneumonia

lobular pneumonia

interstitial pneumonia

The anatomical classification may give a great help to the etiological

diagnosis some times.

> 90% lobar pneumonia: caused by Streptococcus pneumoniae

(pneumococcus) ;

interstitial pneumonia are caused by virus or mycoplasm.

Bacterial Pneumonia

Lobar pneumonia

Def. an acute bacterial infection resulting in fibrinosuppurative consolidation

of a large portion of a lobe or of an entire lobe.

often seen in previously healthy young adults.

• Symptoms: abrupt onset, high fever, shaking chills, pleuritic chest pain, a

productive mucopurulent cough ( “rusty” sputum )

Etiology

• pathogens： streptococcus-pneumoniae, pneumobacillus

• inducing factors: cold, excessive tired, anethesia

Pathogenesis

• bacteria---alveoli---proliferate , capillary dilate, serious exudates---kohn’s

pores---spreading entire lobe

Morphology

For purposes of description, it is convenient to divide the

process into four phases:

(1) Congestion (1st-2nd day)

(2) Red hepatization (consolidation) (3rd-4th day)

(3) Gray hepatization (5th-6th day)

(4) Resolution (1 week)

1. Congestion stage (1st-2nd days)

the outpouring of a protein-rich exudate into alveolar spaces

and rapid proliferation of bacteria.

grossly:

heavy, red, boggy

A frothy blood-stained fluid can be squeezed from the cut surface.

LM:

alveolar wall: cap. dilate, congestion

alveolar space: proteinaceous edema fluid, few neutrophils,

RBC , and numerous bacteria.

Clinically: the onset is sudden with fever and rigors.

2. Red hepatization stage (3rd-4th day)

grossly:

the lobe distinctly red, firm, and airless with a liver-like consistency

LM:

• Septal capillaries are congested markedly

• Alveolar spaces are packed with many red cells, and several

neutrophils, fibrin

• the pleura usually demonstrates a fibrinous or fibrinopurulent

exudates.

3. Gray hepatization stage (5th –6th day)

grossly:

• gray-brown and more solid, liver like consistency

• Pleural surface is covered with a confluent fibrinous exudates.

• The cut surface is dry and granular but of a grayish-white color.

LM:

• Congestion of septal capillaries lightens.

• The fibrinous exudate persists within the alveoli and a fibrin net

forms.

• There are many neutrophils but is relatively depleted of red cells in

the alveoli.

4. Resolution stage (7th-9th day)

the resorption of exudate and enzymatic digestion of inflammatory

debris, with preservation of the underlying alveolar wall architecture

Gross:

softening, volume

LM:

WBC fibrin absorbed

Complication

1. pulmonary carnification:

hypoexudation of neutrophils---proteinase defficiency/ over-exudation of

fibrin---organization of the intra-alveolar exudate convert areas of the

lung into solid fibrous tissue.

2. Tissue destruction and necrosis may lead to abscess formation.

3. Suppurative material may accumulate in the pleural cavity, producing

purulent pleurisy and empyema.

4. Septicemia or pyemia:

Bacteremic dissemination may lead to meningitis, arthritis, or infective

endocarditis.

5. Infective shock:

Failure of terminal circulation and appearance of toxic symptoms.

Pulmonary carnification

Lobar pneumonia（carnification）

Lobular pneumonia

(Bronchopneumonia)

Conception: Defined as an acute purulent inflammation characterized by

diffuse patchy pneumonic consolidation often with bronchiolitis in its center.

clinic: infants, the aged, and those suffering from chronic debilitating

illness or immunosuppression.

• children: Whooping cough and measles are important antecedents

adult: influenza, chronic bronchitis, alcoholism, malnutrition, and

carcinomatosis are all predisposing conditions.

• patchy distribution, a purulent inflammation that centered bronchioles.

Etiology and pathogenesis

• Pathogens: staphylococci, pneumococci, streptococci, influenzae

haemophilus

• Induce factors: cold, heart failure

• Infection ways: respiratory tract, blood

Morphology

gross:

• patchy consolidation through one lobe, more often multilobar and

frequently bilateral and basal

• 0.5-1cm,gray-red to yellow, slightly elevated, poorly delimited at

the margins

Severe: confluent bronchopneumonia

(1) a suppurative, neutrophil-rich exudates centered the bronchi,

bronchioles, adjacent alveolar spaces

(2) walls of bronchioles and alveoli: congestion,edema

(3)surrounding: hyperemic edematous compensative emphysema

(4)the abscesses are marked by necrosis of the underlying architecture

LM:

（1）respiratory failure

（2）heart failure

（3）pyemia

（4）abscess

（5）bronchiectasis

complication

• Hypostatic pneumonia

The patient with pulmonary edema from cardiac failure or heavy uremia, et al, is particularly vulnerable.

• Aspiration pneumonia

The patient in coma or apoplexy, heavy anesthesia and so on is particularly vulnerable.

Viral pneumonia and mycoplasmal

pneumonia

They both belong to interstitial pneumonia

Def. an inflammatory process involving the interstitial tissue

of the lungs.

Etiology and pathogenesis

pathogens:

Most common: influenza virus A/B

Less common: parainfluenza,

respiratory syncytial virus ( especially in infants and children)

Adenovirus common in army recruits

Mycoplasmal pneumonia common among children and young adults

Others: measles, chickenbox

Attachment of the organisms to the respiratory epithelium is followed

by necrosis of the cells and an inflammatory response. Then, the

inflammation extends to the interstitial tissue including peribronchial

connective tissue and interalveolar septa.

Morphology

Macroscopically:

red-blue, congested, volume slightly enlarge and subcrepitant.

little inflammatory exudates escapes on sectioning of the lung

Histologically:

the inflammatory process is largely confined within the walls of the alveoli.

The septa are widened and edematous with a mononuclear infiltrate of

lymphocytes, histiocytes and occasionally plasma cells.

alveolar spaces are remarkably free of cellular exudate

In virus infection, inclusion bodies may be formed within cytoplasm

or nucleus of the epithelial cells of bronchioles and alveoli. In severe

cases alveolar damage with hyaline membranes may develop.

viral inclusion body is round or oval shape, erythrocyte-like in size, eosinophilic

cytoplasmic or nuclear

TYPES of PNEUMONIA

LOBAR BRONCHO-

PNEUMONIA Interstitial

Distribution One or two lobes Scattered Scattered

Cause Strept.Pneumoniae Multiple Bacteria Influenza/Mycoplasma

Pathology Inflammation in

alveolar wall cause

consolidation.

Pleuritis

Inflam & purulent

exudate in alveoli.

Often from

previous process

Interstitial inflam.

Around alveoli.

Necrosis of bronchial

epithelium

Onset Sudden and acute Insidious Variable

Signs High fever & chills

Productive cough

with rusty sputum.

Progressive Rales to

absence of sounds in

affected lobe

Mild fever.

Productive cough

with yellow-green

sputum. Dyspnea

Variable fever,

headache. Aching

muscles.

Nonproductive hacking

cough

TYPES of PNEUMONIA

BRONCHOPNEUMONIA LOBAR PNEUMONIA

Tuberculosis

a communicable chronic granulomatous disease caused by

Mycobacterium tuberculosis.

After HIV, tuberculosis is the leading infectious cause of death in the world.

Infection with HIV makes people susceptible to rapidly progressive

tuberculosis; over 50 million people are infected with both HIV and M.

tuberculosis.

The lung is the most often affected organ .

Basic pathological changes

TB is a special type of inflammation.

• Alteration

• Exudation

• Proliferation

Alteration

• Grossly :

• gray- yellowish, massive

caseation, consolidated

• Microscopically :

red strained homogeneous

amorphic material with cell

debris sometimes or slightly

granular material.

Caseous necrosis

Caseous necrosis

Exudative changes

• Early infections, numerous mycobecteria, high bacteria

virulence, low host immunity and pronouned hypersensitivity.

• • Sero-fibrinous inflammation, neutrophil cells, macrophages

• Location: lung , pleurea,

Few organisms, low virulence and high host immunity.

tubercle——the most characteristic changes in tuberculosis

Proliferation

Tubercle (tuberculous granuloma)

Typical tubercle consists of caseous necrosis in the center, surrounding it

by the epithelioid and some Langhan’s giant cells, with a peripheral

aggregation of small lymphocytes and fibroblasts.

The tubercle can be isolated or fuse to a large one.

the epithelioid cells show a pale pink granular cytoplasm with indistinct

cell boundaries, often appearing to merge into one another. The nucleus is

less dense than that of a lymphocyte (vesicular), is oval or elongated and

may show folding of the nuclear membrane.

Epithelioid cells

Tubercle nodules surrounding fibrosis

Langhans giant cell

Fate of the tuberculosis

Healing of tuberculosis lesion

• — Absorption and resolution.

• — Fibrosis, fibrous encapsulation and calcification.

Exacerbation of tuberculous lesions

• — Infiltration and progression.

• —Dissolution and dissemination.

primary tuberculosis

secondary tuberculosis

Primary pulmonary tuberculosis

• the first infection TB

•more frequent in children, so called the childhood type TB,

but primary lesion may also occurs in adult at a low rate of

the tuberculosis.

Pathology

•Characteristic : Primary complex (the Ghon complex).

— Primary lesion (Ghon focus)

— Tuberculous lymphangitis

— Tuberculous lymphadenitis (in the hilar lymph nodes)

•X-ray : dumbbell-like

Swelling of lymph nodes with caseous necrosis

Primary focus with

Caseous necrosis

Primary pulmonary tuberculosis is usually asymptomatic or

manifested as a mild flu-like illness.

Clinical features

—In 95% of cases, immunity stops disease progression and healing

occurs.

small focus: resolution, fibrosis

large focus: fibrous capsulation, calcification

—In 5% of cases, rapidly progressive pulmonary disease causing

extensive caseous consolidation of the lung, usually occurs only in

malnourished or immunodeficient children.

The fate of primary pulmonary TB

Three routes of dissemination

1.Bronchial dissemination----multiple foci

2.Lymphatic dissemination---hilar peribronchial

cervical even distant lymph nodes

3.Hematogenous dissemination----miliary

disease in lung or generalized military tuberculosis

Blood-borne dissemination: miliary tuberculosis

Acute systematic/pulmonary miliary tuberculosis Numerous pale, translucent nodules in millet size are seen in lungs, kidneys,

liver etc.

Chronic systematic/pulmonary miliary tuberculosis

Secondary pulmonary

tuberculosis

Characteristic •second infection •adults •bronchial dissemination •infection from the apex downwards •the course is usually protracted •combination of old and fresh lesions •proliferation is main lesions

Six types

• Focal pulmonary tuberculosis

• Infiltrative pulmonary tuberculosis

• Chronic fibro-cavernous pulmonary TB

• Caseous pneumonia

• Tuberculoma

• Tuberculous pleuritis

1. Focal tuberculosis

• The earliest lesions.

• most common site: lung apex

• number: one or more

• size: 0.5-1cm

• shape: well circumscribed, grayish white, yellow

• nature: mostly proliferative with central caseous necrosis and

peripheral fibrosis

• Usually asymptomatic

• may calcify or quiescent form of infection or change into other

types

2. Infiltrative pulmonary tuberculosis

(subclavicular lesion):

• most common type, Sputum infection-open TB

• (1)site: upper part of the lungs (subclavicular infiltration)

• (2)serofibrinous exudative lesions with central caseous necrosis

• (3) X-ray ： cloudiness

• (4) tuberculous toxic symptoms and chronic cough, frequently with

hemoptysis easily cured and short clinical course

outcome

a: healing

b: progressive:

enlargement, liquefaction, cavitation

• bronchogenic spread—caseous pneumonia

• breaks through pleura-Pneumothorax，tuberculosis

pyopneumothoraxtransform into chronic fibro-cavernous TB

3. Chronic fibro-cavernous pulmonary TB

(1) The upper lobes of lung contains multiple variant sizes,

thick-walled chronic cavities. (2) Thicked cavity wall -- three components

a. caseous necrosis

b. tuberculous granulation tissue

c. fibrous tissue

(3) coexisting bronchial disseminated many tuberculous lesions and

diffuse fibrosis in the pulmonary tissues.

Later period, the lung becomes small, indurated,with pleural extensive

adhesion, the function of the lung may be severely damaged.

Tubercle cavity

Old foci of TB

New foci of TB

Clinical feature •Toxic：fever, night-sweat

•Respirator：cough, expectoration, hemoptysis, dyspnea, asphyxia

•breaks through pleura-Pneumothorax, pyopneumothorax

•fibrosis -Cor Pulmonale

4. Caseous pneumonia

May occur in debilitated immunodeficient or highly sensitized

patients.

Dissemination of large numbers of organisms in the focus via the

bronchial tree, and spreading rapidly throughout large areas of

lung parenchyma and producing a diffuse bronchopneumonia or

lobar exudative consolidation (“galloping consumption”).

Pathological feature

1. Rapid serious condition of TB progression

2. One lobe or an entire lung affected and become consolidation

3. Severe exudation and severe necrosis

4. Serous exudate contain monocytes and lymphocytes in the alveoli

5. Young patients are more frequently affected

5. Tuberculoma

•Definition: solitary globular caseous lesion surrounded by fibrosis

•Size: 2-5cm in diameter.

•Site: well delineated upper lobe

•X-ray: it is easily mistaken for tumor

•Tuberculomas represent quiescent disease.

tuberculoma

6.Tuberculosis pleuritis

According affected feature divide into:

Moist tuberculous pleuritis (exudative tuberculous pleuritis)

• exudative inflammation (serious or serofibrinous).

• Heavy serious liquid→hydrothorax.

heavy fibrin formation→thoracalgia.

Dry tuberculous pleuritis (proliferative tuberculous pleuritis)

• This is a proliferative lesion dominate.

• Localized tubercles may form in the visceral pleura, and this may be

followed by an tuberculous focus beneath pleura.

Respiratory tumors

• Nasopharyngeal carcinoma

• Laryngocarcinoma

• Pulmonary carcinoma

Pulmonary carcinoma

（Bronchogenic carcinoma）

95% of primary lung tumors arise from the bronchial

epithelium. Undoubtedly, the bronchogenic carcinoma is the

number one cause of cancer related deaths in industrialized cities.

Etiopathogenisis

• Smoking

• Air pollution

• Vocational factor

• Molecular genetic change

Morphology

Types of gross:

central type

periphery type

diffuse type

• Early stage pulmonary carcinoma:

tumor mass <2cm, limited intrabronchi or infiltrated the bronchial wall and

surrounding tissue, no metastasis in LN.

• Occult (concealed) carcinoama:

cytologic smeares of sputum :tumor cells(+),

clinic and X-ray(-),

biopsy showed carcinoma in situ or early infiltrative carcinoma

no metastasis in LN

Histologic classification (2003 WHO):

• squamous cell carcinoma

• small cell carcinoma

• adenocarcinoma

• large cell carcinoma

• adeno-squamous carcinoma

• sarcomatoid carcinoma

• carcinoid tumor

• salivary gland type carcinoma

Squamous cell carcinoma

• More common in men than women

• Tend to arise centrally in major bronchi and eventually spread to local

hilar nodes

• Disseminate outside the thorax later than other histologic types

• Undergo central necrosis, cavitation

• Often preceded for years by squamous metaplasia/ dysplasia in the

bronchial epithelium—carcinoma in situ

• Atypical cells may be identified in cytologic smears of sputum or in

bronchial lavage fluids or brushings, although asymptomatic and

undetectable on radiographs

squamous carcinoma

Small cell lung carcinoma(SCLC)

The five-year survival rate is only 1 to 2%.

Derived from neuroendocrine cells of the lung, express a variety of

neuroendocrine markers.

Nests and cords of round to polygonal cell with scant cytoplasm,

granular chromatin, and inconspicuous nucleoli.

Adenocarcinoma

More common in women, and the association with smoking is weaker than

for squamous cell carcinoma.

usually peripherally located.

grow slowly and form smaller masses than do other subtypes, but

metastasize widely at an early stage.

Bronchioloalveolar carcinoma (BAC)

A special type of adenocarcinoma.

BAC has a better prognosis than other bronchogenic carcinoma, the

localized single mass has a 50 to 70% five-year survival rate, and the

multifocal variant has a 20 to 25% five-year survival rate.

Large cell carcinoma

• A group of neoplasm that lack cytological differentiation and

probably represent squamous carcinoma or glandular neoplasms

that are too undifferentiated to permit categorization.

• Have a poor prognosis because of their tendency to spread to distant

sites early. five-year survival rate is 2 to 3%.

Large cell carcinoma

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