Bronchogenic carcinoma

DR AYMAN EL-DIB
Pulmonary Tumors

Benign Malignant
• Harmartomas • Metastasis
• Primary
– Bronchogenic
– Bronchial
Carcinoid
– Pleural
Mesotheloma
Metastatic Lung Cancer
Primary Lung Cancer

• Breast • Melanoma
• GI Tract • Sarcoma
• Kidney

"Cannon Balls"
Five Leading Annual
Causes of Death
• Heart Disease (32%)
• Cancer (23%)
• CVD (7%)
• COPD (5%)
• Accidents (4%)
 USA Cancer Deaths
Males - 280,000
• Pulmonary - 92,000 (30%)
• Prostate - 35,000 - (13%)
• Colorectal - 28,500 (10%)
Females - 254,000
• Pulmonary - 58,000 (23%)
• Breast - 44,000 (17%)
• Colorectal - 30,000 (12%)
 Bronchogenic Carcinoma
• Number 1 cause of Ca deaths in both men
and women
• Rate decreasing in males
• Rate increasing in females & more virulent
• M:F is 2:1
• Peak incidence is 40 to 70 years
• Male smokers x 10 to die from Ca than
non-smokers
 Cigarette Smoking &
Bronchogenic Carcinoma
Statistical - relationship between dose
(pack-years) and lung Ca frequency.

Clinical - progressive alterations in

respiratory tract epithelium and cigarette
smoke.

Experimental - mutagens, carcinogens, but

no good experimental model.
 Pathophysiology
Non–small cell lung cancer (NSCLC)
Accounts for approximately 75% of all lung cancers.divided into :
Adenocarcinoma, 35-40% of all lung cancers (the most
frequent)
Squamous cell carcinoma, 25-30% of all lung cancers) .
Large cell carcinoma, 10-15% of lung cancers
All share similar treatment approaches and prognoses but have
distinct histologic and clinical characteristics.
Small cell lung cancer (SCLC)
Account for approximately 20-25% of all lung cancers.
Exhibits aggressive behavior, with :
Rapid growth,
Early spread to distant sites,
Exquisite sensitivity to chemotherapy and radiation,
Frequent association with distinct paraneoplastic syndromes
Bronchogenic CA - Common
Morphologic Features
• Most arise from bronchial epithelium near
hilus
• All associated with cigarette smoking -
SCC, SCLC
• All aggressive locally invasive, widely
metastasizing to liver (40%), brain (20%),
and bones (20%)
• Ability to synthesize bioactive products
Non-Small Cell Carcinoma
Squamous Cell Carcinoma (SCC) (40%)
• More common in men than women
• Arise centrally in bronchi, disseminate
later
• Preceding squamous metaplasia to CIS
• Obstruction
Adenocarcinoma (20%)
• Most common in women, nonsmokers, < 40y
• Peripheral location, associated with scars
• Slow growing but metastasize early
Non-Small Cell Carcinoma
Bronchoalveolar Carcinoma (5%)
• Peripheral single or multiple nodules
• Tall columnar with cell papillary growth
• Solitary lesions are surgically resectable
(25% survival)

Large Cell Carcinoma (10%)

• Difficult to categorize
• Metastasizes early
Small Cell Lung Carcinoma
• Smokers
• More common in men than women
• Centrally located with early extension
• Rapidly growing, early to metastasize
• Wide variety of paraneoplastic
syndromes (neuroendocrine)
• Poorer survival than N-SCLC
Lung Cancer - Clinical Presentation

• Silent till metastasis to brain, liver, bone, or

node: Approximately 10% of patients with
lung cancer are asymptomatic and their
cancers are diagnosed incidentally after a
chest radiograph (CXR)
 Lung cancers manifestation
1-Constitutional symptoms
Fatigue Anorexia , Weight loss
2-Symptoms due to primary tumor
Central tumors are generally squamous cell carcinomas &
SCLC :
- Cough, Hemoptysis, - Dyspnea, Wheezing,
- Atelectasis, Postobstructive pneumonia,
Most peripheral tumors are adenocarcinomas or large cell
carcinomas and produce symptoms of:
- Cough and dyspnea,
- Symptoms due to pleural effusion
- Severe pain as a result of infiltration of parietal pleura &
the chest wall.
 Lung cancers manifestation
• 3-Symptoms due to distant spread
• Neurological dysfunction (ie, brain metastasis, spinal cord
compression)
– Bone pain (bone metastasis)
– Abdominal/right upper quadrant pain
( liver, suprarenal metastasis).
• 4-Symptoms due to intrathoracic spread :
• Superior vena cava obstruction,
• Dysphagia resulting from esophageal compression;
• Stridor (ie, compression of the trachea mainstem bronchus)
• Paralysis of the recurrent laryngeal nerve, causing
hoarseness
• Phrenic nerve palsy, causing paralysis of the diaphragm;
5-Horner syndrome; Superior sulcus tumors
Pressure on the sympathetic plexus, and brachial
plexus, resulting in intense, radiating neuropathic pain in
the upper extremity.
6-Paraneoplastic syndromes
Most paraneoplastic syndromes are caused by SCLC .
Squamous cell carcinomas are more likely to be
associated with hypercalcemia due to parathyroid like
hormone production.
Clubbing and hypertrophic pulmonary osteoarthropathy
and the Trousseau syndrome of hypercoagulability are
caused more frequently by adenocarcinomas.
 Lung Cancer - Local
Symptoms
• Pneumonia due to bronchial obstruction
• Horner's Syndrome - invasion of inferior
cervical ganglion
• Superior Vena Caval Syndrome
• Recurrent Laryngeal nerve involvement
(hoarseness)
• Phrenic nerve involvement (hiccups,
diaphragm paralysis)
• Pleural effusion
 Lung Cancer – Radiological
• CXR: Diagnosis
• Can be used to monitor response to therapy if
it is clearly visible and measurable.
• Popcorn calcification is usually a radiologic
characteristic of benign lesions.
• CT scan and MRI:
• Because common sites of spread include the
liver and adrenals, a CT scan of the chest and
upper abdomen, is the minimum standard for a
staging workup for a person newly diagnosed.
• CT scan or MRI of the brain may be required if
neurological symptoms or signs are present.
Most thoracic surgeons perform imaging of the
brain before attempting definitive resection of a
lung malignancy.
 Lung Cancer – Radiological
Diagnosis
• Bone scintigraphy:
• The skeletal system is another common site of metastases for lung cancers.
• If patients report bone pain or serum calcium or alkaline phosphatase levels
are elevated, a bone scan should be obtained to search for bone
metastases.
• Positron emission tomography
• PET scanning is approved by (FDA) for the workup of solitary lung nodules.
• Recent studies suggest that PET scanning is useful for searching for
systemic spread if other diagnostic modalities cannot clarify an abnormality
that may change the treatment of the patient's condition. However, false-
positive and false-negative results can occur.
• PET scans appear to be more sensitive, specific, and accurate than CT
scans for staging mediastinal disease. PET scans often detect
abnormalities not demonstrated on CT scans. Staging may be influenced by
PET in up to 60% of pts
Lung Cancer – Lab. Diagnosis
• Sputum cytologic studies
– Centrally located endobronchial tumors exfoliate malignant cells
(positive in 40%).
– A positive finding for malignancy from a cytologic specimen is
accurate in as many as 90% of cases, but any distinction
between different histologic subtypes is not accurate.
• CBC count:
– Cytopenias;
– Additionally, before instituting initial full-dose combination
chemotherapy :
• Absolute neutrophil count should be >3000 / L,
• Hemoglobin >10 g/dL,
• Platelet count >100 x 103/ L
Serum chemistries:
– Elevated serum calcium and alkaline phosphatase
raise the suspicion of bone metastasis,
– The presence of hyponatremia is considered an
adverse prognostic indicator.
– Elevated serum lactate dehydrogenase (LDH)
indicates increased tumor mass and cell turnover
and is an adverse prognostic indicator.
 Procedures
Bronchoscopy
When a lung cancer is suggested, especially if
centrally located, bronchoscopy provides a means for :
Direct visualization of the tumor,
Allows determination of the extent of airway
obstruction,
Allows collection of pathologic material under
direct visualization.
Diagnostic material can be obtained with
Direct biopsy of the visualized tumor,
Bronchial brushings and washing,
Transbronchial biopsies.
 Procedures
– Mediastinoscopy:
• This is usually performed to evaluate the status of
enlarged mediastinal lymph nodes before attempting
definitive surgical resection of lung cancer.
– Thoracoscopy:
• This is usually reserved for tumors that remain
undiagnosed after bronchoscopy or CT-guided biopsy.
• Thoracoscopy is also an important tool in
the management of malignant pleural
effusions
 CT-guided biopsy:

This procedure is preferred for tumors located in the periphery of the lungs
because peripheral tumors may not be accessible through a bronchoscope.
Biopsy of other sites:

Diagnostic material can also be obtained from other abnormal sites eg,
Enlarged palpable lymph nodes,
Liver,
Pleural and pericardial effusions.
Thoracentesis:

For adequate staging, pleural effusions should be aspirated and examined for
malignant cells if no other sites of distant spread are identified. Presence of malignant
pleural effusion upstages the disease to extensive stage.

If a large symptomatic pleural effusion is present, therapeutic thoracentesis provides

symptomatic relief.
In patients with resistant, relapsed, or nonresponding disease, thoracentesis can be
combined with pleurodesis to prevent recurrence.
The preferred agent currently is Sterilized Talc, which can be instilled either as slurry
or as a powder during pleuroscopy.
 Lung Cancer - Diagnosis

• Cytology of expectorated sputum (50% FN)

• Bronchoscopy: 90% for endobronchial
lesions 50% for peripheral lesions
• CT - fine needle cytology >80% for malignant
lesions
 Staging of Small Cell Carcinoma of Lung

Stage Description

Limited Disease confined to one hemithorax;

stage includes involvement of mediastinal,
contralateral hilar, and/or supraclavicular
and scalene lymph nodes.
Malignant pleural effusion is excluded.

Extensive Disease has spread beyond the definition of

stage limited stage, or
Malignant pleural effusion is present.
1-Chemotherapy
Only 33% of patients with NSCLC present with sufficiently localized disease at diagnosis
to attempt curative surgical resection (stages IA and IB, IIA and IIB, and IIIA).
Approximately 50% of patients who undergo surgical resection experience local or
systemic relapse; thus, approximately 80% of all patients with lung cancer are
considered for chemotherapy at some point during the course of their illness.
Chemotherapy alone has no role in potentially curative therapy for NSCLC. NSCLC is
only moderately sensitive to chemotherapy. it may be used as:
Adjuvant chemotherapy (ie, chemotherapy given after surgery)may reduce the
relapse rate after surgical resection of localized NSCLC
Neoadjuvant chemotherapy (ie, chemotherapy given prior to surgery) may
prolongs survival in subjects with stage IIIA disease.
Part of Multimodality therapy for locally advanced NSCLC and is used alone in the
palliative treatment of stage IIIB and stage IV NSCLC.
Some newer agents have shown promising single-agent activity. Combination
chemotherapy regimens have been reported to achieve response rates as high as
50%, especially when newer agents are included.
• 2-Radiation therapy
• Radiation therapy may be used as:
– Radical alone in the treatment of stage I and stage II NSCLC,
only when surgical resection is not possible because of limited
pulmonary reserve or the presence of comorbid conditions.
– Adjuvant therapy after resection of the primary tumor.
– Palliative therapy: for relieve of symptoms as SVC obstruction
and pain.
– Local therapy has been associated with improvement in 5-year
survival rates in early-stage NSCLC.
• 3-Combined chemoradiotherapy
• The current standard of care of good-risk (ie, Karnofsky
performance score of 70-100, minimal weight loss)
patients with locally advanced NSCLC is combined-
modality therapy consisting of platinum-based
chemotherapy and radiation.
• These results in statistically significant improvement in
both disease-free and overall survival rates compared
with either modality used alone
 .
5- Surgical Care:
Surgical resection provides the best chance of long-term disease-free survival and
possibility of a cure.
In stages I and II NSCLC, surgical resection is almost always possible unless comorbid
medical conditions are present or the patient's respiratory reserve is so low.
The role of surgery for stage IIIA disease is controversial. Patients with stage IIIB or IV
tumors are generally not surgical candidates.
Preoperative evaluation:
This should include :
Careful assessment of respectability,
Cardiopulmonary reserve,
Perioperative risk.
Pulmonary function tests: As a general guideline :
Patients with FEV1> 2.5 L are able to tolerate pneumonectomy.
Patients with FEV1of 1.1-2.4 L, a lobectomy is possible.
Patients with FEV1of < 1 L, patients are not considered candidates for surgery.

These factors are further modified by the presence of cardiac disease or other comorbid
conditions.
Surgical procedures:
The standard surgical procedures for lung
cancer include
Lobectomy
Pneumonectomy.
Wedge resections are associated with
an increased risk of local recurrence
and a poorer outcome.
Complications:
The perioperative mortality rate is :
6% for pneumonectomy,
3% for lobectomy,
1% for segmentectomy.
 Lung Cancer Survival

• Overall survival is less than <10%

• Less than 30% can be operated on
• SCC if untreated; survival is in the order
of weeks - with treatment - months.
 NSCLC Lung Cancer -
Survival

• 1/3 metastatic or non-resectable at

presentation
• 1/3 inoperable because of
cardiopulmonary status
• 1/3 operable for cure
SCLC Lung Cancer -
Survival

•Almost all metastatic at presentation

•Survival is measured in weeks to
months
 Paraneoplastic Syndromes
Symptom complexes other than cachexia that
can't be explained by local or distant spread or
by hormones indigenous to the tissue of origin.
•Occurs in 10-15% of cancer patients
•May represent early manifestations of occult
cancer
•May be significant & even lethal
•May mimic metastatic disease
Paraneoplastic Syndromes
& Bronchogenic Carcinoma
Mechanism Cell (Usual) Syndrome
PTH-RP Squamous Hypercalcemia
Not Cell
osteolytic lesions

Chorionic Large Cell Gynecomastia

gonadotropin

Small Cell Ectopic ACTH Cushing's

Syndrome
Paraneoplastic Syndromes
& Bronchogenic Carcinoma

Cell (Usual) Syndrome

Mechanism
All but SCLC Pulmonary
Unknown
Osteoarthropathy

AdenoCa Thrombophlebitis
Unknown