Jerel D.

Marquez MD - 11 11/21/2016
Group 14
LUNG CANCER

Case

A 39-year-old, Caucasian male is complaining of ischemic chest pain that has been
persisting for a month. Chest pains worsen with deep breaths, and become more
painful on the left side than right side. The patient states that he has painful
coughing that has progressively gotten worse in the past two weeks with
hemoptysis that started one week ago. The patient also complains of difficulty
breathing for the past two weeks.

The patient complains of chest pain that has worsened over the past 3-4 weeks. The
pain is located in the thoracic region and has worsened acutely. Patient describes
the pain to be relatively constant throughout the day and night, and varies in
severity, and rates the pain as 7/10 at its worst. In addition to chest pains, patient
complains of dysphagia. Patient has taken a week off from work because he feels
constantly fatigued and tired. Upon speaking, patient becomes short of breath and
needs to take deep breaths to continue conversation. When patient takes deep
breaths in between conversation, a wheezing sound is produced. Hoarseness of
patients voice is evident. The patient has a persistent chronic cough that has
persisted two weeks, and the cough produces sounds that can be considered as
smokers cough.

Physical Exam Findings

The patients respiratory system is examined. Using a stethoscope, the patients

chest is examined, and there did not seem to be fluid buildup around the lungs in
the pleura, therefore, there is no indication of lung failure or collapse. The patients
respiratory rate is 25 per minute. During bilateral auscultation, an abnormal high-
pitched sound can be heard on inspiration and expiration. Therefore, slightly
narrowed airways can be detected, possibly due to a blockage. In addition, the
patients heart sounds were distant on auscultation. Upon percussion of the thoracic
cavity and both lungs, a hypo-resonance is produced from the tapping of both lung
fields, suggesting a possible tumor in the lungs. During the consultation, the patient
was strenuously coughing, and was spitting out phlegm. Blood was present in the
patients sputum.

The patients lymphatic system was examined. Upon palpation of the trachea and
surrounding lymph nodes, a slight deviation of the trachea is present. This can
possibly be due to the notably tender, enlarged lymph nodes in the supraclavicular
and cervical region, as well as marginally swollen axillary lymph nodes. Lymph node
metastasis is suspected due to the enlarged lymph nodes and the patients evident
hoarse voice.

Clinical Procedures
A bronchoscopic biopsy was performed, and the pathologic (microscopic)
examination of the cells from the lesion in the left hilar revealed small cell lung
cancer cells. A biopsy of the upper thoracic lymph nodes revealed metastasis to the
thoracic lymph nodes of the upper mediastinum. The bronchoscopy using
Jerel D. Marquez MD - 11 11/21/2016
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fluorescence examined the trachea and major airways of the lung for abnormalities,
but no major blockages were identifiable.

A frontal chest x-ray disclosed a markedly large 50 mm diameter, round mass on

the left hilum. In addition, an increased opacity is shown in the left paratracheal
region of the lungs, suggesting a mass is present in the paratracheal region.
Multiple pulmonary nodules are shown on the ipsilateral upper and middle lung. The
nodule opacities on the radiograph indicate metastatic deposits and possible
lymphadenopathy. The frontal chest radiograph shows a slight widening of the
mediastinum in the superior left region of the lungs.

A contrast-enhanced CT of the head, chest, and abdomen reveals a lesion on the

superior left lobe with infiltration to the bronchi and trachea. The computed
tomography scan of the chest confirmed the 35 mm diameter, round tumor in the
left lung. A transverse slice of the lungs shows a large white spot, and small lesions
on the left lung. The CT scan of the head and chest also showed enlargements in
the mediastinal lymph nodes and subclavicular lymph nodes. A biopsy of the
enlarged lymph nodes proves that the lung cancer has metastasized to the lymph
nodes proximal to the lungs.

The result of a sputum cytology test of the patients sputum is positive for
carcinogenic cells. A microscopic examination of the cancer cells from a sputum
(mucus coughed up from the lungs) smear showed that the cells appeared to be
blue, round, and small (approximately twice the size of lymphocytes). This suggests
that the submucosal layer of the bronchus have been affected by small cell lung
cancer.

Small-cell lung carcinoma (SCLC, 15% of all lung cancer) and non-small-cell lung
carcinoma (NSCLC, 85%) are the two major forms of lung cancer. Non-small-cell
lung cancer is further classified into squamous-cell carcinoma, adenocarcinoma,
and large-cell carcinoma.

Pathogenesis
Jerel D. Marquez MD - 11 11/21/2016
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Morphology
Gross:
o Respiratory system
Distal atelectasis and postobstructive pneumonia
With pleural effusion
o Cardiovascular system
Pericardial effusions that may be asymptomatic when small, but
may result in tamponade if large or accumulated over a short
period
With equalization of pressures in cardiac chambers
May have presence of superior vena cava (SVC) obstruction
o Central nervous system
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Asymptomatic brain metastases occuring in 5-10% of patients

with SCLC.
Mass lesions with surrounding brain edema
o Gastrointestinal system
Liver common site of metastatic spread.
May have icterus (secondary to widespread liver metastasis or
obstruction of biliary outflow) and/or hepatomegaly
o Lymphatic system
May have enlarged ipsilateral supraclavicular lymph nodes
(limited-stage disease)
Enlarged axillary lymph nodes (extensive-stage disease).

Arising centrally in this lung and spreading extensively is a small cell anaplastic (oat cell)
carcinoma. The cut surface of this tumor has a soft, lobulated, white to tan appearance. The
tumor seen here has caused obstruction of the main bronchus to left lung so that the distal lung
is collapsed. Oat cell carcinomas are very aggressive and often metastasize widely before the
primary tumor mass in the lung reaches a large size.

Microscopic:

Small-cell carcinoma is an undifferentiated neoplasm composed of primitive-appearing cells.

As the name implies, the cells in small-cell carcinomas are smaller than normal cells, and barely
have room for any cytoplasm.
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Clinical Presentation
Respiratory system
o Shortness of breath
o Use of the accessory muscles of respiration (scalene muscles,
intercostal muscles)
o Flaring of the nasal alae
o Dullness to percussion
o Decreased or absent breath sounds on the side of the effusion
Cardiovascular system
o Shortness of breath
o Heart sounds may be distant on auscultation
o Elevated jugular venous pulsation with paradoxical rise with
inspiration.
o Pulsus paradoxus
o Cardiac catheterization reveals equalization of pressures in cardiac
chambers.
o Clubbing, cyanosis, or edema of extremities
o Right upper extremity usually edematous
Central nervous system
o Raised intracranial pressure secondary to mass lesions and
surrounding brain edema
o Physical findings depend on the site of the brain lesions
Gastrointestinal system
o No specific finding related to the gastrointestinal (GI) tract on
examination
Lymphatic system
o Enlarged ipsilateral supraclavicular lymph nodes
o Enlarged axillary lymph nodes upstage the diagnosis to extensive-
stage disease.
Jerel D. Marquez MD - 11 11/21/2016
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METASTATIC LUNG CANCER

Metastatic lung cancer occurs when lung cancer cells break away from a tumor
and travel to other parts of your body through the blood or lymph system. The Lung
is the most common site of metastatic neoplasm. Lung cancer can be metastatic at
the time of diagnosis or following treatment. Because symptoms do not develop
when lung cancer is present, it is common for the cancer to metastasize before it is
diagnosed.

Pathophysiology
The mechanisms through which cancer spreads to the lungs are direct extension
and true metastatic spread through the bloodstream, airway, or lymphatic system.
Iatrogenic implantation of a primary tumor is exceedingly rare.

Direct extension
Cancer spread through direct extension is not frequently encountered and most
commonly includes direct invasion by a primary neoplasm, involving a contiguous
organ or structure (eg, thyroid, esophagus, thymus, chest wall), or spread from a
neoplasm metastatic to another intrathoracic structure (eg, rib or mediastinal lymph
node, commonly causing an obstructive lesion of the trachea or bronchus).
Direct extension can also occur through a vascular route, such as the spread of
renal cell cancer or testicular germ cell cancer as a tumor thrombus to the lung via
the inferior vena cava and the right side of the heart.

Metastatic spread
True metastases occur via the pulmonary arteries or bronchial arteries, via the
pulmonary lymphatics, across the pleural cavity, or, infrequently, via the airways.
Arterial
o The pulmonary arteries are the most common route for metastases.
Cancers most likely to metastasize to the lungs include those with a
rich vascular supply draining directly into the systemic venous system.
Spread via bronchial arteries may be responsible for some
endobronchial metastases. (Other proposed modes of endobronchial
spread include bronchial invasion from parenchymal lesions, spread via
involved mediastinal or hilar lymph nodes, and extension along the
proximal bronchus.)
Lymphatic
o Lymphangitic spread can occur in association with hematogenous
dissemination, which is subsequently followed by invasion of the
adjacent interstitium and lymphatics, with subsequent tumor spread
toward the hila or toward the periphery of the lung.
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o Lymphangitic spread can also occur via retrograde spread of a tumor
from the originally affected mediastinal or hilar lymph nodes, with
consequent obstruction of lymphatic flow.
Pleural
o Pleural spread most frequently results in pleural metastases in the
caudal and posterior parts of the pleural cavities.
Airway
o Spread via airways is rare and difficult to prove, except in the case of
broncho-alveolar carcinoma.

Morphology
Gross

Variably-sized nodules of metastatic carcinoma in lung.

Microscopic
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Examples of the histomorphology of the four main types of lung cancer: a) squamous cell
carcinoma (p63, CK5/6); b) adenocarcinoma (TTF1, CK7); c) large cell carcinoma. These
three main types constitute the group of nonsmall cell lung cancers. d) Small cell carcinoma
(synaptophysin, chromogranin, CD56/NCAM).

Clinical Presentation
Patients with multiple pulmonary nodules as a result of metastatic spread can
be asymptomatic, especially those with indolent, slow-growing cancers, such
as papillary thyroid cancer or adenoid cystic carcinoma of the salivary gland.
However, the clinical presentation of patients with pulmonary metastatic
lesions occurring late in the course of advanced extrapulmonary cancer is
commonly dominated by the signs and symptoms of advanced/terminal
malignant disease and by signs and symptoms associated with the primary
cancer.
Lymphangitic spread of the cancer into the lungs is associated with the recent
onset of rapidly progressive dyspnea at rest and, occasionally, dry cough.
This pattern is usually encountered in patients with a known history of
cancer, most commonly of the breast, stomach, pancreas, or prostate.
Endotracheal and endobronchial metastases can be associated with new-
onset cough, shortness of breath, and, occasionally, hemoptysis and chest
pain.
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Atypical pneumonia was first applied to viral community-aquired pneumonias

(CAP) that were clinically and radiologically distinct from bacterial CAPs. Over the
past decades, atypical pneumonia has come to mean lower respiratory tract
infections due to specific respiratory pathogens, i.e., Chlamydia psittaci
(psittacosis), Francisella tularensis (tularemia), Coxiella burnetii (Q fever),
Chlamydia pneumoniae, Mycoplasma pneumoniae or Legionella species. The newly
recognised causes of CAP, i.e., severe acute respiratory syndrome (SARS),
hantavirus, and avian influenza, are not considered atypical pneumonias, but
should be regarded as viral CAPs

The most common atypical pneumonias are caused by three zoonotic pathogens,
Chlamydia psittaci (psittacosis), Francisella tularensis (tularemia), and Coxiella
burnetii (Q fever), and three nonzoonotic pathogens, Chlamydia pneumoniae,
Mycoplasma pneumoniae, and Legionella. These atypical agents, unlike the typical
pathogens, often cause extrapulmonary manifestations. Atypical CAPs are systemic
infectious diseases with a pulmonary component and may be differentiated
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clinically from typical CAPs by the pattern of extrapulmonary organ involvement
which is characteristic for each atypical CAP

Pneumonia any infection of the lung parenchyma

o Happens when pulmonary anti-microbial defense mechanisms are
impaired or the systemic resistance of the host is lowered.
o Factors affecting resistance of the host:
Chronic diseases
Immunologic deficiency
Treatment with immunosuppressive agents
Leukopenia
o Factors that compromise the local defense mechanisms of the
lung:
Loss or suppression of the cough reflex result of coma,
anesthesia, neuromuscular disorders, drugs, or chest pain (may
lead to aspiration of gastric contents)
Injury to the mucociliary apparatus due to:
Impairment of ciliary function or destruction of ciliated
epithelium
o Cigarette smoking
o Inhalation of hot or corrosive gases
o Viral diseases
Genetic defects of ciliary function
o Immotile cilia syndrome
Accumulation of secretions in conditions (e.g. cystic fibrosis,
bronchial obstruction)
Interference with the phagocytic or bacterical action of alveolar
macrophages by alcohol, tobacco, smoke, anoxia, or oxygen
intoxication
Pulmonary congestion and edema

Etiology
Community Acquired Bacterial Pneumonia
o Determined by:
Host reaction
Extent of involvement
Specific etiologic agent
o Predisposing factors:
Extremes of age
Chronic diseases (congestive heart failure, COPD, and DM)
Congenital or acquired immune deficiencies
Decreased or absent splenic function (sickle cell disease or post
splenectomy - encapsulated bacteria such as pneumococcus)
Community Acquired Viral Pneumonia
o Factors that favor extension of infection:
Age
Malnutrition
Alcoholism
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Underlying debilitating illness

Pathogenesis
Community Acquired Bacterial Pneumonia
o Upper respiratory tract viral infection
o Bacterial invasion of the lung parenchyma
o Alveolar filling of inflammatory exudate causing consolidation
(solidification) of pulmonary tissue
o Tissue destruction and necrosis causing abscess formation (common
with type III pneumococci or Klebsiella infections)
o Spread of infection to pleural cavity, causing intrapleural
fibrinosuppurative reaction (empyema)
o Bacteremic dissemination to heart valves, pericardium, brain, kidneys,
spleen, or joints, causing metastatic abscesses, endocarditis,
meningitis, or suppurative arthritis
Community Acquired Viral Pneumonia
o Viral tropism allows viruses to attach to and enter the respiratory lining
cells (pneumocytes)
Hemagglutinin serves to attach the virus to its cellular target
via sialic acid residues on surface polysaccharides
Uptake of virus into endosomal vesicles
Acidification of the endosome
Conformation change in hemagglutinin, allowing fusion of
the viral envelope with the host membrane
Release of viral genomic RNAs into cytoplasm of the cell
Neuraminidase facilitates the release of newly formed virions
budding from infected cells
Cleaving of sialic acid residues
o Viral replication and gene expression
o Cytopathic changes, inducing cell death and secondary inflammation
Inhibition of sodium channels, producing electrolyte and water
shifts, leading to fluid accumulation in alveolar lumen
Inhibition of host cell mRNA translation and activation of
caspases leading to apoptosis.
Exacerbation of of fluid accumulation releasing danger signals
that activate resident macrophages
Release of inflammatory mediators (chemokines and cytokines)
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Activation of pulmonary endothelium, allowing neutrophils to
attach and extravasate into interstitium
o Damage and impairment of local pulmonary defenses (impairment of
mucociliary clearance)
o Secondary bacterial superinfections

Morphology
Community Acquired Bacterial Pneumonia
o Two patterns of anatomic distribution:
Lobar pneumonia consolidation of a large portion of a lobe or
of an entire lobe of the lung
Lobular bronchopneumonia patchy consolidation of the
lung
May become confluent, producing a virtually total lobar
consolidation
o Bronchopneumonia foci are consolidated areas of acute
suppurative inflammation
More often multilobar, but may be confined to one lobe
Frequently bilateral and basal tendency of secretion to
gravitate to the lower lobes
With slightly elevated, dry, granular, gray-red to yellow, poorly
delimited at the margins, well developed lesions
Histologically: reaction elicits a neutrophil rich exudate that
fills the bronchi, bronchioles, and adjacent alveolar spaces
Community Acquired Viral Pneumonia
o Mucosal hyperemia and swelling
Plugging of the nasal channels, sinuses or Eustachian tubes
Suppurative secondary bacterial infection
o Lymphomonocytic and plasmacytic infiltration of the submucosa
o Overproduction of mucus secretions
o Interstitial inflammatory reaction involving walls of the alveoli
Widened and edematous alveolar septa with mononuclear
inflammatory infiltrates of lymphocytes, macrophages, and
plasma cells
Alveoli may be free of exudate but may have intraalverolar
proteinaceous material and cellular exudates

Gross:
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A. Bronchopneumonia. Section of the lung showing patches of consolidation (arrows).

B. Lobar pneumonia grey hepatization. The lower lobe is uniformly consolidated

Microscopic:

Bacteria Legionella pneumophilia, a gram-negative bacillus or rod involved with Legionnaires

Disease
Jerel D. Marquez MD - 11 11/21/2016
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Streptococcus pneumoniae remains the most commonly identified pathogen in community-
acquired pneumonia

Clinical Presentation
Laboratory Tests:
o C-reactive protein and procalcitonin elevation if bacterial in etiology
(rather than in viral).
Community Acquired Bacterial Pneumonia
o Abrupt onset of high fever
o Shaking chills
o Cough producing mucopurulent sputum
o Hemoptysis
o Pleuritis pleuritic pain and pleural friction rub
o Focal opacities in radiographic diagnostics
o Treatment: antibiotic administration
Community Acquired Viral Pneumonia
o May have absent cough
o Fever
o Headache
o Muscle aches
o Pains in the legs
o Ventilation and blood flow mismatch due to edema and exudation
o Treatment: self-limiting, supportive management