Lesions of the upper respiratory tract. Pulmonary infections

Respiratory System
Ist
Practical Pulmonary
Pathology
A Diagnostc Approach 2005
Rhinitis
• Allergic
• Infectious
• Chronic
Allergic rhinitis
• Also called hay fever
• Due to exposure to plant pollens, fungi,
dust mites, animal allergens
• IgE mediated hypersensitivity reaction
type I.
Infectious rhinitis
Also called “common cold”
Due to adenovirus, echovirus and rhinoviruses
Symptom: catarrhal discharge
Chronic rhinitis
Sequel to acute rhinitis with development of
secondary bacterial infection
Associated with deviated septum or nasal polyps
Nasal polyps
Common;
non-neoplastic, allergic
reaction
Micro: edematous
lamina propria with
variable inflammatory
infiltrate including
eosinophils
Nasopharyngeal carcinoma
Nasopharyngeal carcinoma
• Demographics vary greatly by region
• In USA: rare, in Africa: common childhood
cancer
• South China: most common cancer in adults
70% male
• Associated with EBV infection
• Histology: squamous cell carcinoma
Inflammatory/infectious lesions
1.Croup - parainfluenza virus
laryngo-tracheo-bronchitis in children
inflammatory narrowing produces inspiratory stridor
2.Diphtheria - Corynebacterium
pseudomembrane
3.H. Influenzae - acute epiglottitis
Tonsillitis - β-hem Strept - rheumatic fever
4.Tuberculosis
LARYNX PAPILLOMA
LARYNX CARCINOMA
Warty outgrowths of laryngeal
surface epithelium
Children
Usually multiple
Associated with
HPV 6 and 11 in most cases
Adults
Usually men, solitary
Recurrences frequently exhibit
dysplasia
DD: verrucous carcinoma
Squamous cell carcinoma
of larynx
96% male; usually ages 40+
Major risk factors are smoking, enhanced by
heavy alcohol consumption
Asbestos exposure(?)
Squamous cell carcinoma
Site influences histology and clinical
behavior – either glottic, supraglottic or
subglottic
• Spread is limited by tough membranes /
ligaments
Metastases to regional lymph nodes and
lungs; direct extension to thyroid gland
and jugular vein
others
Vocal cord polyp
• Also called laryngeal nodule or singer’s
nodule
• Noninflammatory response to injury due to
changing air pressure
Vocal Cords
Trachea
decubitus
tracheitis
bronchitis
bronchiolitis
pneumonia
Lung diseases
• Acute lung injury (ARDS)
• Inflammation: pneumonia
nota bene: pneumonitis – non-organic
hypersensitive reaction
• COPD (chronic obstructive lung disease)
• Restrictive lung diseases
DPLD (diffuse parenchymal lung disease)
• Neoplasma- primary & secondary
Acute Respiratory Distress Syndrome
(Diffuse Alveolar Damage)
ARDS
DAD
ARDS is the end result of acute alveolar injury caused
by a variety of insults and probably initiated by different mechanisms.
The initial injury is to either the capillary endothelium or alveolar epithelium.
increased capillary permeability
interstitial and then alveolar edema
fibrin exudation
formation of hyaline membranes
Organization and scarring follows.
Endotoxin, neutrophils and macrophages
may also play key roles in the pathogenesis of ARDS.
Pneumonia
•
•
•
•
Clinical data: acute – chronic
Pattern: broncho – lobar
Clinical feature: atypical – hypostatic etc …..
Type of infection: community - acquired (out of
hospital) hospital– acquired nosocomial,
opportunistic
• Based on agents: bacterial, viral,fungal …
• Host reaction: normal, immunocompr, illness,
infants, elderly…
Pneumonia
Bronchopneumonia:
Patchy consolidation of the lung centered on
bronchi
Lobar pneumonia:
Affects entire lung but now rare due to
antibiotics; associated with increased
virulence of organism or increased host
vulnerability (infants, elderly)
(Pneumococcus)
broncho-
lobar -
Atypical pneumonia
Mycoplasma pneumoniae
others:
respiratory syncytial virus, rhinovirus, rubeola, varicella,
Chlamydia psittacosis, Coxiella burnetti (Q fever)
interstitial pneumonia (usually) or bronchopneumonia
Often asymptomatic
• Micro: bronchiolitis, interstitial and minimal intra-alveolar
involvement with widened alveolar septa due to
lymphoplasmacytic inflammatory cells
Legionella pneumonia
• also Legionellosis or Legion Fever
• Legionella pneumonia is known as legionnaire’s disease and
this is an acute respiratory infection on that is caused by the
legionella pneumophila bacteria (Gram neg. Bacillus).
• Immune-suppressed, organ transplanted patients!!!!
• The bacteria are found in the water delivery systems and can
survive in warm and moist air conditioning systems.
The first recognized cases of Legionnaires' disease occurred
in 1976 in Philadelphia. Among attendees of a Legionnaires'
convention held at the Bellevue-Stratfor Hotel 182
Legionnaires contracted the disease and 29 of them died.
Aspergillus
Causes fungus balls in immunocompetent
patients with microabscesses or multinucleated
giant cells in the lung
Mucoid impaction – in bronchial tree
Systemic aspergillosis
Grocott
Abscess
Due to sinobronchial infections,
• dental sepsis,
• aspiration
• primary bacterial infection (Staphylococcus
aureus, Klebsiella pneumonia, Streptococcus
pneumonia),
• fungi,
• neoplasia induced obstruction
Aspiration induced abscesses more common on
right side
Air fluid level present if there is communication with
air passages
Air fluid level present if there is communication
with air passages
Tuberculosis
Mycobacterium tuberculosis hominis & bovis
obligate aerob
most common cause of death due to infacted diseases
vector: drops, contamination
pathogenesis: cell- mediated immunity: ~ 3 weeks
after the primary contamination
resistency and the allergic reaction develop together
(type IV, late)
mediator :TH1 cell
the immunerespons causes destruction in the lung
parenchyma (necrosis, caverna)
Tuberculosis
Type of inflammation:
chronic specific
granulomatous
inflammatory
lesion
w/wo
necrosis
primary tbc – primary infection
secunder tbc – already sensibilized patient
localizes espec in the apical parts of lung –
followed by caverna
lymphatics – right heart – pulmonary arterial
dissemination– miliary tbc
systemic or localized organic tbc
Tuberculosis
• Diagnosis:
appearance of
bacteria with acid-fast
stain,
• positive smears or
cultures; 1 bacillus in
a 1 cm3 granuloma
indicates the
presence of 2000 Ziehl-Neelsen
organisms
Culture
PCR
Apical focus, caverna
tuberculosis
Wegener’s granulomatosis
• Triad of necrotizing
angiitis, aseptic
necrosis of upper
respiratory tract and
lungs, focal
glomerulonephritis
• c-ANCA positive in 90%
(Cytoplasmic antineutrophil
cytoplasmic antibodies)
• Gross: well
circumscribed lesion
with necrotic
appearance
Respiratory System
2nd
Chronic Obstructive Pulmonary
Disease (COPD)
Major symptom is dyspnea • Obstructive airway
disease: increase in
• Usually due to cigarette
resistance to airflow due
smoking
to obstruction at any
(bronchitis,emphysema)
level;
Site of disease:
bronchi- chronic bronchitis, • reduced maximal airflow
rates (FEV1)
bronchiectasis, asthma;
bronchioles-bronchiolitis,
acini- emphysema
Chronic Bronchitis
• Diagnosis: persistent cough with sputum for 3 months in
2 consecutive years
• More infections, purulent sputum, hypercapnia, hypoxia
than emphysema; clinically called “blue bloaters”
• Causes: 4-10x more common in smokers, also chronic
irritation, infections
Reid index:
ratio of thickness of
mucus gland layer to
thickness of wall
between epithelium and
cartilage;
normal is 0.4, increased
in chronic bronchitis
Chronic Bronchitis
• Simple bronchitis: mucoid sputum wo obstruction
• Intermittant bronchial spasmus
• Chronic obstructive bronchitis w emphysema (heavy
smokers)
„blue blusters”
Hypercapnia and Cyanosis
Emphysema
• Permanent enlargement of air spaces
distal to terminal bronchiole with wall
destruction but without fibrosis
• Acinar and airspace enlargement is
usually due to tobacco related wall
destruction
Emphysema
Pathogenesis
Oxidants
and
Free Radicals
Proteases
(elastase)
Emphysema subtypes
Α-1antitrypsin
(A1AT) def.
smoking
TB:terminal
bronchiolus
RB:resp.bron
chiolus
AD:alveolar
duct
AS:alv. sack
1.
2.
Chronic Obstructive Diseases of the Lung
[ACP Medicine 2004. © 2004 WebMD Inc.All rights reserved.]
1.Centriacinar
2.Panacinar
3.Paraseptal
4.Irregular
near to scar
A1ATD and Smoking
Medicine » Pulmonology » "COPD Clinical Perspectives", book edited by
Ralph J. Panos, ISBN 978-953-51-1624-0, Published: July 16, 2014 under CC
BY 3.0 license. © The Author(s). NE:neutrophil elastase
Emphysema
Subtypes
centriacinar (smoking)
panacinar
(α-AT deficiency)
distal acinar
irregular
proteases & oxidants
activity
„pink puffers”
dyspnoe & hyperventillation
emphysema
Asthma
• reversible bronchoconstriction
• atopic: TH2 and IgE mediated immunologic reaction to
allergens characterized by acute and late-phase
reactions
• non-atopic: viral infections and air pollutants
• eosinophils are key inflammatory cells
• basement membrane thickening and hypertrophy of
smooth muscle of bronchi
CURSCHMANN'S SPIRAL
Spiral shaped mucous plug
in asthma patients
Bronchiectasis
• Bronchial obstruction
• Cystic fibrosis
• Chronic (necrotizing)
infection of bronchi and
bronchioles associated
with permanent
dilatation of these
airways
• Symptoms: cough, fever,
purulent sputum
• Sec amyloidosis!!!!
• Gross:
markedly distended
peripheral bronchi,
usually in lower lobes,
can trace to pleural
surface;
Kartagener Syndrome
• Situs inversus, bronchiectasis and sinusitis, due
to defective ciliary action
Diffuse Interstitial (restrictive)
Lung Disease (DPLD)
reduced expansion (compliance) of lung
parenchyma with decrease in total lung
capacity;
normal FEV1
fibrosing diseases
• interstitial / infiltrative lung diseases - ILD
interstitial fibrosis
• pneumoconioses
granulomatous diseases (sarcoidosis)
Diffuse Pulmonary
(restrictive)
Lung Disease (DPLD)
Rtg & CT
Normal lung
Fibrosing diseases
Idiopathic pulmonary fibrosis (rare!!)
(usual interstitial pneumonia - UIP)
• 60+ (male>female)
• recurrent alveolitis
• Diagnosis of exclusion
(no asbest, no vascular
disease etc)
Non-specific interstitial pneumonia
Fibrosis
Pneumoconioses
silicosis
coal-worker’s pneumoconiosis
asbestosis
(talcosis, siderosis, aluminosis, berylliosis)
definition
dust in the lung
diseases of the lung related to the inhalation of the dust
inorganic dusts
granulomatous reaction and fibrosis
silicotic lung
a.
b.
c.
Fibrotic nodules
Progressive massive fibrosis
Alveolar proteinosis
Coal worker's pneumoconiosis (CWP)
a. Primary macules are less than 7 mm
b. Nodular lesions are up to 2.0 cm
c. Progressive massive fibrosis
Asbestosis
The histologic changes vary from bronchiolocentric fibrosis to
honeycomb lung.
An asbestos body consists of a central core fiber of asbestos that is
coated with an iron-protein-mucopolysaccharide laye. Iron stains
e.g. Prussian blue, can make detection easy.
Granulomatous inflammation
(non-infectious)
Boeck’s sarcoidosis
• Multisystemic disease of
unknown origin that involves
lung in 90% of cases
• 65% recover without further
problems; 20% have
permanent pulmonary loss;
• Skin: erythema nodosum
•
• Presents as bilateral hilar
lymphadenopathy (BHL)
diagnosis of exclusion,
culture and special stains
• Treatment: steroids for severe
symptoms, advanced disease
Diff dg!!!!!!!
complications
Regardless of the etiology for restrictive
lung diseases, many eventually lead to
extensive fibrosis.
complications
Both restrictive and obstructive lung diseases
can affect the pulmonary arterial circulation.
The loss of normal lung parenchyma leads to pulmonary hypertension
that leads to thickening of the small arteries.
Lung transplantation
27% chronic obstructive pulmonary
disease (COPD), including emphysema;
16% idiopathic pulmonary fibrosis;
14% cystic fibrosis;
12% idiopathic (formerly known as
"primary") pulmonary hypertension;
5% alpha 1-antitrypsin deficiency;
2% replacing previously transplanted
lungs that have since failed;
24% other causes,
including bronchiectasis and sarcoidosis.
Respiratory System
3rd
Pulmonary tumors
Benign Neoplasms
Hamartoma
Soiltary Fibrous Tumor
rare
Desmoid Tumor
Carcinoid Tumorlets
Sclerosing Hemangioma
Adenomas
Salivary Glandlike tumors
Mesenchymal Tumors
Squamous cell
papilloma
HPV 6, 11
ISH
carcinoma
in situ
severe dysplasia
(premalignant,
reverzibie
surgical
specimen
non-small cell
cancer
(85%)
Stage
TNM
occult
TXN0M0
0
TisN0M0
IA
T1N0M0
IB
T2N0M0
IIA
operability
~20%!!!!!!!!!
T1N1M0
IIB
T2N1M0
T3N0M0
IIIA
T1N2M0
T2N2M0
T3N1M0
T3N2M0
IIIB
any of T, N3M0
T4, any of N, M0
IV
any T és N, M1
Tobacco Smoking!!!!!
risk factors
Asbestos
Radon
Cancer-causing Agents
in the Workplace
Radiation Therapy to the Lung
- uranium
arsenic, beryllium. vinyl chloride, nickel chromates,
coal products, mustard gas, and chloromethyl ethers
fuels such as gasoline
diesel exhaust
Marijuana
Marijuana contains more tar than cigarettes.
Recurring Inflammation
Talc and Talcum Powder
Other Mineral Exposures
Diet
- low in fruits and vegetables
may increase the chances of getting cancer
if you are exposed to tobacco smoke.
Copyright 2006 © American Cancer Society, Inc.
Published August 3, 2010 | By Dr Gadgeel
endobronchial pictures of lung cancer
grossly
central
squamous
peripherial
adenocarcinoma
central and peripherial
peribronchial
small cell
Pancoasttumor
compression of
cervical ganglia
Horner triad
ptosis, enophthalmus, miosis
characteristic but not specific
Metastatic properties
lymphatic, lymph nodes
hematogen
brain
bones, liver, adrenal glands
skin, serous membranes
GI Neoplasms
Bone Tumors
Breast Cancer
Renal Cell Carcinoma
Prostate
Malignant Melanoma
sclc
nsclc
small cell lung cancer
non-sclc
neuroendocrine
anaplastic
squamous (SCC)
adenocarcinoma (ADC)
large cell carcinoma
tobacco smoking
tobacco smoking
SCC & ADC
Kulschitzky (?)
stem cell (?)
SCC – metaplasia
ADC – pneumocyte II
stem cell (?)
chemo
surgical- and/or radiochemo
cell type
risk factor
cell type of
origin
therapy
sclc
nsclc
SCC
p63
hormone actvity (ACTH)
ADC
BAC
TTF1
Immunehistochemistry
LCC
paraneoplastic syndromes
BAC:bronchioloalveolar carcinoma - in situ ADC
Genomic
landscape in
lung cancers
Non-small cell cancer pathway
Molecular targeted therapy
for NSCLC
Gefitinib (Iressa™, ZD-1839)
Erlotinib (Tarceva™, OSI-774)
Michihiko Kuwano
Professor, Dean, Faculty of Medical Sciences
EGFR:Epidermal Growth Factor Receptor
TKI: Tyrosine Kinase Inhibitor
carcinoid
neuroend
typical/atypical
chromogranine
mucoepidermoid
adenoid cystic
Salivary glandlike
malignant tumors of
main brochi
pleura
ptx
hydrothorax
pleural effusion
hemothorax
tumor
primary/metastatic
ptx
Haemothorax
Pneumothorax
Hydrothorax
lung
punction
Rheumatoid
arthritis
Fibrinopurulent
pleuritis
mesothelial cells
lymphoma
mesothelioma
EMA
pleural fluid
TTF-1
lung ADC
tuberculotic
pleuritis
asbestosis
Pleuroscopic – malignant mesothelioma
mesothelioma
diffusum
HE
VATS biopsy:
mesothelioma
calretinin
Thanks!