The Respiratory System

lect-9&10
 Cancers of the Respiratory Tract

 Carcinoma of the Larynx

 It is of squamous cell carcinoma.
 < 2% of all cancers
 Smoking
 Chronic alcohol intake, HPV and asbestos
inhalation.
 Ulceration of mucosa
 Hoarseness, loss of voice
 Good prognosis
 5-year survival rate 75%
Tumors of the lung
 90-95% are bronchogenic carcinoma.
 5% Carcinoid.
 2-5% mesenchymal and other miscellaneous
neoplasms.
 Lung Cancer-Bronchogenic
carcinoma
 1/3 of all cancers in US.
 1/3 of all cancer deaths in males.
 Over 7% of all deaths in both sexes.
 90% of sufferers are smokers.
 free radicals, other carcinogens in smoke
 5-year survival rate 10-15%.
 Aetiology and pathogenesis

 Role of tobacco smoke:

 Strong relationship between the smoking and
BC:
 :statistical evidence -1

 Average smokers have ten fold increase risk of

cancer than non smoker.
 Heavy smoker have 20 fold increase risk of cancer
(40 cig./d. fro several years).
 It depends on amount of daily smoking, tendency to
inhale and duration of smoking habit.
 Cessation of smoking for 10 years reduces risk.
 Causes cancer of lip, tongue, floor of mouth,
pharynx, larynx, esophagus, urinary bladder and
pancreas.
:Clinical evidence -2

 By observation of histologic changes

in the lining epithelium of the
respiratory tract in smokers which
causes a lot of atypical cells.
 :Experimental work -3

 There is more than 1200 known materials in

smoke, some are initiators (as polycyclic
aromatic hydrocarbons, including
benzopyrene) and promoters as phenol
derivatives, & radioactive elements as
polonium 210, carbon-14, potassium40. Also
there is contaminants as nickel, arsenic,
molds and additives.
 Protracted exposure to these additives to
mice causes skin cancer.
:Role of industrial hazards
 Radiation (atomic bombs survivors in H & N show
high incidence of bronchogenic carcinoma). Also
the Uranium miners have a 4 fold increased risk
and about 10 times increased risk if smoker.
 Asbestos workers also have a 5 fold increased risk
and if smokers 90 fold increased risk with a latent
period may reach to 10—30 years. It also causes
pleural and peritoneal mesotheliomas, with
gastrointestinal carcinoma.
 Nickel, Chromate, Arsenic, Beryllium, Iron,
newspaper workers, gold miners and halo-ether
workers.
 Role of air pollution
 Inhalation and bronchial deposition of
radioactive decay products that
become attached to environmental
aerosols.
 :ROLE OF GENETIC FACTORS
 Some genetic predisposition.
 Genetic variation of inducible enzyme activating
some carcinogens in cigarette smoke.
 Some familial clustering.
 Dominant oncogene c-myc in small cell carcinoma.
 K- ras in adenocarcinoma.
 Deleted recessive gene P53 and Retinoblastoma
gene.
ROLE OF SCARRING:
Near scars, adenocarcinoma.
Scar occur as a result of old infarct, metallic foreign
bodies, wounds & granulomatous infections.
Classification
 Several microscopic classifications, most widely
used (kreyberg):
 1- Squamous cell carcinoma:
 a- well differentiated, b- moderately, c- poorly.
 2- Adenocarcinoma:
 a- Not otherwise specified (NOS).
 b- Bronchioalveolar.
 3- Adenosquamous carcinoma.
 4- Small cell carcinoma:
 a- Classic. b-Mixed small cell/large cell. c-combined
 5- Undifferentiated large cell carcinoma.
 6- Giant cell carcinoma.
 :Morphology
 GROSS:
 Most often near hilus, ¾ occur in 1st, 2nd and 3rd order bronchi.
 Usually start in in thick area of in situ carcinoma and then
progress to small mass, irregular, that erode the lining
epithelium. Then it fungates into lumen forming intra-luminal
mass.
 It can also rapidly penetrate the wall of the bronchus and
peribronchial tissues, carina, mediastinum.
 It is solid, gray-white, with some areas of necrosis,
hemorrhage and even central necrosis and cavitation.
 Extension to pleural surface with effusion.
 Extend then to tracheal, bronchial and mediastinal lymph
nodes (in 50%).
 Distant dissemination along lymphatics and blood stream is
common an there is no organ exception. Adrenals is involved
in more than half of cases? Liver in 30-50%, brain 20% bone
20%.
Cavitary scc
Solid peripheral ca.
 Microscopy
 SQUAMOUS CELL CARCINOMA:
 Most in men, smoking related, large tumors, central,
spread locally and late metastasis.
 It has high rate of growth, and nearby squamous
metaplasia and dysplasia is seen.
 ADENOCARCINOMA:
 NOS is bronchial derived, most common type in
women, in nonsmokers, peripherally located, small,
solid, slowly growing, with little mucin.
 Bronchioalveolar type arise from terminal bronchioles,
which form either single or multiple nodules produces
pneumonia like consolidations, with tall columnar cells
line the alveolar septa in numerous papillary formations
and better prognosis.
Nearby abnormal mucosa
Tad pole cell in sputum
Epithelial pearl of concentric cells
adenocarcinoma
Adenocarcinoma-in p.l.
Bronchioalveolar
Bronchioalveolar
With invasion
Large cell carcinoma
:Small cell carcinoma
 Highly malignant, small cells, with little cytoplasm,
round or oval nuclei as the shape of lymphocytes
(but it is double size) = classic oat cell. Some are
spindle shape or polygonal.
 EM: show dense core neurosecretory granules, so
able to secrete polypeptide hormones.
 Positive immunohistochemical stains are neuron
specific enolase, parathormone like products.
 Strong relationship to smoking.
 Most often hilar or central and most aggressive type,
metastasize widely and incurable by surgical means
and associated with ectpoic hormone secretions.
Oat cell carcinoma
Moulding in sputum malignant cells
Oat cell carcinoma
High mitotic rate in oat c.c.
Neurosecretory granules in EM
Bone invasion with moulding
Bone marrow invasion
Brain and meninges invasion
Small cell carcinoma with mixed type
:Large cell carcinoma
 Anaplastic type with large cells totally undifferentiated with high
cellular atypia.
 May see giant cells in the same type or separated into single
group of giant cell carcinoma.
SECONDARY PATHOLOGY:
 Partial obstruction may cause marked focal emphysema.
 Total obstruction may lead to atelectasis, impaired drainage
causes severe suppuration with ulcerative bronchiectasis, or
abscess.
 Compression or invasion of superior vena cava causes venous
congestion, dusky head and arm edema =superior vena cava
syndrome.
 Extension to pericardial or pleura sacs may cause pericarditis or
pleuritis with effusions.
Staging of NSCLC
 TNM classification
 Consistent, reproducible
description of the extent of
disease
 Identifies groups of patients with
similar prognosis and therapies
 Analysis of outcomes
TMN Classification of Lung Cancer

Tumor (T)
TX Occult cancer (cells in sputum/washings but no tumor seen by imaging studies or
Bronchoscopy)
T1 Tumor < 3 cm surrounded by lung / visceral pleura, not proximal to lobar bronchus
T2 Tumor > 3 cm, or involvement of main bronchus 2 cm distal to carina or with pleural
invasion, or atelectasis / obstructive pneumonia extending to hilar region
T3 Tumor invading chest wall, diaphragm, mediastinal pleura, of parietal pericardium; or
tumor within 2 cm of carina; or atelectasis of entire lung
T4 Tumor invading mediastinum, heart, great vessels, trachea, esophagus, vertebral body,
or carina, or ipsilateral pleural effusion, satellite nodule within same lobe
Nodes (N)
N0 No regional lymph node metastases
N1 Metastases to ipsilateral peribronchial or hilar nodes
N2 Metastases to ipsilateral mediastinal or subcarinal nodes
N3 Metastases to contralateral mediastinal or hilar or to any scalene or supraaclavicular nodes
Distant Metastases (M)
M0 No distant metastases
M1 Distant metastases
Staging Groups for Lung Cancer
Stage T N M
Occult Tx N0 M0
Stage I A T1 N0 M0
Stage IB T2 N0 M0
Stage IIA T1 N1 M0
Stage IIB T2-3 N0-1 M0
Stage IIIA T3 N1 M0
T1-3 N2 M0
Stage IIIB T4 N0-2 M0
T1-4 N3 M0
Stage IV Any T Any N M1
CLINICAL FEATURES - Thoracic
Symptoms-most are of local effects
Centrally located lesions
 Cough, stridor, wheezing, hemoptysis, dyspnea, and
chest pain
 Superior Vena Caval Syndrome
Peripheral
 Chest pain, cough, and dyspnea (rib invasion)
Large peripheral tumors
 May present as lung abscesses
Intrathoracic extension
 Recurrent laryngeal nerve - hoarseness
 Esophagus – dysphagia
 Pericarditis, tamponade.
 CLINICAL FEATURES
.Thoracic Symptoms-cont
Pancoast syndrome - Superior sulcus tumor
 Local extension at apex of lung
 Involves 8th cervical / 1st thoracic nerve
 Ipsilateral shoulder / arm pain
 Phrenic nerve invasion: diaphragm paralysis.
 Horner’s syndrome
 Paravertebral extension and sympathetic nerve
involvement
 Enophthalmos, ptosis, meiosis, and ipsilateral
anhidrosis
Para-neoplastic Syndromes
NSCLC
 Cachexia, PTH/hypercalcemia, hypertrophic
pulmonary osteoarthropathy, and
neurologic syndromes
SCLC
 Weight loss, anorexia, neuromyopathies
 ADH, ACTH, Calcitonin, PTH
 PTH-like peptide: hypercalcemia
 ACTH excess (Cushing Syndrome)
 ADH excess (Edema)
Clubbing of fingers
Solitary Pulmonary Nodule
Definition
 Size (1 - 4 cm)
 Small, spherical density / surrounded
by lung parenchyma
Incidence of Malignancy
 Geographic location
 30 - 50%
Solitary Pulmonary Nodule
Etiology
 Neoplasms
 Benign
 Malignant
 Infectious
 Granulomas
 Systemic diseases
Solitary Pulmonary Nodule
 Malignant nodule
 Doubling time - 30 to 400 days
 Size > 3 cm (>80%)
 CT enhancement > 20HU

 Benign nodule
 Stable > 2 yrs
 Coin lesion by x ray.
 Mostly hamartoma.
 Presence of calcifications
Lung Cancer Chest X-Ray

Initial stages
not detectable
on chest X-rays

X-ray ca
Diffuse interstitial ca. + R. diap.
Hilar tumor + LN
Neuroendocrine tumors-bronchial Carcinoid

 1-5 % of all lung tumors.

 90% of bronchial adenomas, which is
old name that include also in 10%
adenoid cystic carcinoma &
mucoepidermoid carcinoma.
 Most are young patients less than 40
years, with no relation to smoking.
:Grossly

 Show neurosecretory granules and

markers.
 finger like or polypoid masses that
commonly project into the lumen.
 Size rarely exceeds 3-4 cm.
 Most confined to main stem bronchus.
 May penetrate wall and form collar
button lesion.
:Microscopically

 Nests, cords and masses of cells

separated by delicate stroma
 Regular cells with uniform round
nuclei and infrequent mitoses.
Lung Cancer

 More lung cancers are result of other tumors

metastasizing in the lung via blood, lymph vessels
 Metastatic tumors
 breast cancer, non-Hodgkin’s lymphoma,
osteosarcoma, neuroblastoma, Wilms tumor.

Almost any cancer can spread to the lungs, and

metastases are found in 20 to 40% of patients
dying of various cancers. The incidence of
metastatic cancer to the lung is 6 out of 100,000
people.
RCC-Hematogenous lung metastasis
Lymphatic lung metastasis-breast
 Pleural diseases
 Most are secondary.
 Primary include:
 1- Primary intrapleural bacterial infections.
 2- Primary neoplasm=mesothelioma.
 Pleural effusion is most common manifestation of both
primary and secondary diseases.
 Normally 15 ml of serous fluid, clear and acellular.
 Increased fluid in:
 1- Increase hydrostatic pressure as R. sided HF.
 2- Increased vascular permeability as pneumonia.
 3- Decreased oncotic pressure as nephrotic syndrome.
 4- Increased intrapleural negative pressure as
atelectasis.
 5- Decreased lymphatic drainage as mediastinal
carcinomatosis.
 Inflammatory pleural effusion
 1- Serous, serofibrinous and fibrinous pleuritis, same
processes.
 Common causes:
 Inflammatory as tuberculosis, pneumonia, lung infarcts, lung
abscess and bronchiectasis.
 Rheumatoid arthritis, SLE, uremia, and other systemic disorders.
 Radiation.
 2- Empyema: purulent pleural exudate.
 As yellow-green creamy pus composed of masses of
neutrophils admixed with other leukocytes.
 May end by organization with dense fibrous adhesions.
 3- True hemorrhagic pleuritis: sanguineous exudate seen in
hemorrhagic diatheses, rickettsial diseases, neoplastic
involvement.
 Non inflammatory pleural effusions
 Called as hydrothorax, clear and straw color,
unilateral or bilateral according to the cause.
 Bilateral in HF, RF, Liver cirrhosis.
 Isolated right sided hydrothorax occurs in Meig’s
syndrome (hydrothorax, ascites, ovarian firboma).
 Local collections seen in adhesions.
 Hemothorax is escape of blood to pleural cavity,
fatal complication of ruptured aortic aneurysm or
vascular trauma, form clot without inflammatory
response.
 If nonfatal, organize and form adhesions.
 Chylothorax: milky fluid usually of lymphatic origin.
 Occur due to thoracic duct obstruction or trauma.
Pneumothorax
 Air or gas in the pleural cavity, spontaneous,
traumatic or therapeutic.
 Caused by emphysema, asthma and
tuberculosis.
 Air resorbed after sealing of opening.
 Spontaneous is idiopathic and occur in young
age.
 Tension Pneumothorax with flap valve.
 Air in pleural cavity.
 Pleural tumors
 Secondary metastatic tumors are more common,
and most from lung and breast, and also ovarian
carcinoma which tends to cause widespread implants
and result in serous or serosanguineous effusions
contain malignant cells seen by cytological
examination of the fluid.
 Primary:
 1- Pleural firboma (benign mesothelioma):
 Localized growth that is often attached to pleural
surface by a pedicle, small 1-2 cm, with no effusion.
 Grossly: dense fibrous tissue with cyst.
 Microscopy: whorls of reticulin and collagen fibers and
fibroblasts.
 :Malignant mesothelioma
 25-45 year exposure to asbestos and has no
relation to smoking.
 Grossly:
 there is wide spread diffuse lesions with
effusion and direct invasion of thoracic
structures.
 Microscopically:
 Mixture of two types of cells, mesenchymal
stromal cells and epithelium like lining cells.
(both are malignant).
Pleural mesothelioma
Malignant and benign mesotheliomas