6nd week theme -...
TRANSCRIPT
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ZHANG WEI (张伟)
Associate Professor, Ph.D.
Institute of Pathology & Forensic Medicine
Department of Pathology & Patho-physiology
Zhejiang University School of Medicine
8-year system Curriculum
6nd Week Theme
Respiratory Diseases
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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
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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
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1. Etiological classification:
bacterial pneumonia
viral pneumonia
fungal pneumonia
mycoplasma pneumonia etc.
Classification of pneumonia
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2. Anatomical classification:
lobar pneumonia
lobular pneumonia
interstitial pneumonia
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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.
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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 )
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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
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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)
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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.
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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.
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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.
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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
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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.
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Pulmonary carnification
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Lobar pneumonia(carnification)
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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.
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Etiology and pathogenesis
• Pathogens: staphylococci, pneumococci, streptococci, influenzae
haemophilus
• Induce factors: cold, heart failure
• Infection ways: respiratory tract, blood
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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
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(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:
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(1)respiratory failure
(2)heart failure
(3)pyemia
(4)abscess
(5)bronchiectasis
complication
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• 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.
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Viral pneumonia and mycoplasmal
pneumonia
They both belong to interstitial pneumonia
Def. an inflammatory process involving the interstitial tissue
of the lungs.
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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
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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.
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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
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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.
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viral inclusion body is round or oval shape, erythrocyte-like in size, eosinophilic
cytoplasmic or nuclear
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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
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TYPES of PNEUMONIA
BRONCHOPNEUMONIA LOBAR PNEUMONIA
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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 .
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Basic pathological changes
TB is a special type of inflammation.
• Alteration
• Exudation
• Proliferation
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Alteration
• Grossly :
• gray- yellowish, massive
caseation, consolidated
• Microscopically :
red strained homogeneous
amorphic material with cell
debris sometimes or slightly
granular material.
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Caseous necrosis
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Caseous necrosis
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Exudative changes
• Early infections, numerous mycobecteria, high bacteria
virulence, low host immunity and pronouned hypersensitivity.
• • Sero-fibrinous inflammation, neutrophil cells, macrophages
• Location: lung , pleurea,
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Few organisms, low virulence and high host immunity.
tubercle——the most characteristic changes in tuberculosis
Proliferation
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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.
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Epithelioid cells
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Tubercle nodules surrounding fibrosis
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Langhans giant cell
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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.
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primary tuberculosis
secondary tuberculosis
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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.
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Pathology
•Characteristic : Primary complex (the Ghon complex).
— Primary lesion (Ghon focus)
— Tuberculous lymphangitis
— Tuberculous lymphadenitis (in the hilar lymph nodes)
•X-ray : dumbbell-like
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Swelling of lymph nodes with caseous necrosis
Primary focus with
Caseous necrosis
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Primary pulmonary tuberculosis is usually asymptomatic or
manifested as a mild flu-like illness.
Clinical features
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—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
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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
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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
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Secondary pulmonary
tuberculosis
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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
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Six types
• Focal pulmonary tuberculosis
• Infiltrative pulmonary tuberculosis
• Chronic fibro-cavernous pulmonary TB
• Caseous pneumonia
• Tuberculoma
• Tuberculous pleuritis
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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
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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
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outcome
a: healing
b: progressive:
enlargement, liquefaction, cavitation
• bronchogenic spread—caseous pneumonia
• breaks through pleura-Pneumothorax,tuberculosis
pyopneumothoraxtransform into chronic fibro-cavernous TB
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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.
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Tubercle cavity
Old foci of TB
New foci of TB
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Clinical feature •Toxic:fever, night-sweat
•Respirator:cough, expectoration, hemoptysis, dyspnea, asphyxia
•breaks through pleura-Pneumothorax, pyopneumothorax
•fibrosis -Cor Pulmonale
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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”).
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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
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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.
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tuberculoma
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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.
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Respiratory tumors
• Nasopharyngeal carcinoma
• Laryngocarcinoma
• Pulmonary carcinoma
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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.
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Etiopathogenisis
• Smoking
• Air pollution
• Vocational factor
• Molecular genetic change
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Morphology
Types of gross:
central type
periphery type
diffuse type
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• 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
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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
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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
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squamous carcinoma
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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.
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Nests and cords of round to polygonal cell with scant cytoplasm,
granular chromatin, and inconspicuous nucleoli.
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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.
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Bronchioloalveolar carcinoma (BAC)
A special type of adenocarcinoma.
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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.
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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%.
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Large cell carcinoma
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Thanks !