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Kent J. Blanke D.O. FACOS Bronchogenic Carcinoma My Rules For Lung Masses I am taught to think the worst. Any lung mass is cancer until proven otherwise!! Epidemiology Etiology/risk factors Pathogenesis Pathology Diagnosis Staging Management Surgical Management Prevention

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kent j blanke d o facos

Kent J. Blanke D.O. FACOS

Bronchogenic Carcinoma

my rules for lung masses
My Rules For Lung Masses

I am taught to think the worst.

Any lung mass is cancer until proven otherwise!!

bronchogenic carcinoma
Epidemiology

Etiology/risk factors

Pathogenesis

Pathology

Diagnosis

Staging

Management

Surgical Management

Prevention

Bronchogenic Carcinoma
quick pearls
Quick Pearls
  • Lung Cancer is the leading cause of cancer death in both men and women in the United States.
  • Bronchogenic Carcinoma is divided into two subgroups: Small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC).
  • Non-small-cell includes adenocarcinoma, squamous cell, and large cell cancers.
quick pearls5
Quick Pearls
  • The correct tissue diagnosis is critical to determine the appropriate therapy.
  • Small cell lung cancer has a high response rate to chemotherapy and radiation, and is rarely treated by surgery alone. It is highly aggressive, and tend to metastasize.
  • Non-small cell lung cancer can be cured by surgery alone in certain stages and is not curable by chemotherapy alone.
epidemiology
Epidemiology
  • Lung cancer is the second most common cancer in the U.S.
  • It accounts for 15% of all cancers.
  • Lung cancer accounts for approximately one-fourth of all cancer deaths.
  • In 2000 the deaths attributed to lung cancer were 160,000, exceeding the combined total deaths of breast, prostate, and colorectal cancer.
epidemiology7
Epidemiology
  • Historically lung cancer predominated in men, however with the increase in smoking rates among women, the estimated male to female ratio is 1.2 : 1
etiology risk factors
Etiology/Risk Factors
  • Cigarette Smoking
  • Asbestos exposure
  • Radon exposure
  • COPD
  • Other carcinogens
cigarette smoking
Cigarette Smoking
  • Cigarette smoking is the most important risk factor in the development of lung cancer.
  • Smokers have a 10-25 fold increase in lung cancer incidence compared to nonsmokers.
  • Cigarette smoking accounts for > 85% of lung cancer seen in the USA.
cigarette smoking10
Cigarette Smoking
  • More than 40 carcinogens have been identified in cigarette smoke, some include: polycyclic aromatic hydrocarbons, nickel, vinyl chloride, aldehydes, catechols, peroxides, and nitrosamines.
  • Smoking cessation causes a gradual drop in lung cancer risk, but not a complete normalization of risk
cigarette smoking11
Cigarette Smoking
  • After 10-15 years of abstinence from smoking the life long risk of lung cancer approximates that of a nonsmoker.
  • Second hand smoke contains a significant amount of carcinogens.
  • Second hand smoke increases the chances of developing lung cancer with a relative risk of 1.3
asbestos exposure
Asbestos Exposure
  • Inhalation of asbestos fibers may cause both pulmonary and pleural malignancies, including bronchogenic carcinoma (all 4 types) and pleural mesothelioma.
  • The relative risk of lung cancer in an asbestos worker is approx. five fold.
  • The lag between time of first exposure to asbestos and the development of cancer ranges from 20-30 years.
radon exposure
Radon Exposure
  • In the US, as many as 30,000 lung cancer deaths may be attributable to radon exposure each year.
  • Mining of radioactive ores was the first occupation to be linked to the development of lung cancer.
  • The alpha particles of radon daughters are believed to deliver significant radiation to bronchial epithelium.
  • Significant radon exposure produces a 15 fold increase in the risk of developing lung cancer
slide14
COPD
  • The presence of COPD defined as either air flow obstruction on PFTs or symptoms of chronic bronchitis increases the risk of lung cancer several fold.
  • COPD is a risk factor by itself and is not just a reflection of the number of cigarettes smoked.
pathogenesis
Pathogenesis
  • The development of bronchogenic carcinoma follows a multi-step carcinogenesis process with the successive accumulation of mutations in a number of genes involved in regulating growth.
  • DNA damage occurs after exposure to carcinogens.
pathogenesis16
Pathogenesis
  • A progression of histologic change occurs.
    • 1. proliferation of basal cells
    • 2. development of atypical nuclei with prominent nucleoli
    • 3. stratification
    • 4. development of squamous metaplasia
    • 5. carcinoma in situ
    • 6. invasive carcinoma
pathogenesis17
Pathogenesis
  • Oncogenes (c-myc, N-ras, c-erbB-2)
  • Tumor suppresor genes ( p53, retinoblastoma gene Rb)
  • Abnormalities of p53 expression occur in up to 100% of SCLC and 75% of NSCLC.
pathology
Pathology
  • There is a slight preponderance of lung cancer developing in the right lung because the right lung has approx. 55% of the lung parenchyma.
  • Lung cancer also tends to develop more commonly in the upper lobes than the lower lobes.
pathology19
Pathology
  • Squamous cell accounts for one-third of all lung cancers. Until recently it was the most common cell type. It has been surpassed by adenocarcinoma which makes up approx. 45%.
  • Large cell accounts for 15-20% of tumors.
  • Small cell makes up 20-25% of primary lung malignancies.
squamous cell
Squamous Cell
  • Squamous cell carcinoma tends to originate in the central airways. It’s origin in the bronchial epithelium explains the occasional occurrence of positive sputum cytology in the absence of chest radiographic abnormalities
adenocarcinoma
Adenocarcinoma
  • Most of these tumors are peripherally located (75%). Tends to metastasize earlier than squamous cell. Due to the peripheral location of these tumors sputum cytology is rarely positive.
  • A subcategory of adenocarcinoma called Bronchioalveolar carcinoma also arises in the periphery. However, this sub type tends to be more indolent and offer a better prognosis. These tumors appear as interstitial infiltrates on radiograph and can be confused with infectious pneumonitis.
large cell
Large Cell
  • The location and behavior of large cell carcinoma is very similar to that of squamous cell carcinoma.
  • Two rare subtypes of large cell are the giant cell carcinoma assoc with peripheral leukocytosis, and clear cell carcinoma which resembles renal cell carcinoma.
small cell
Small Cell
  • Approximately 80% originate centrally.
  • They tend to expand against the bronchus causing extrinsic compression.
  • These tumors spread rapidly to regional hilar nodes, mediastinal lymph nodes, and distant sites especially bone marrow and the brain.
diagnosis
Diagnosis
  • Management of Solitary Pulmonary nodule
  • Symptomatic Presentation of Cancer Patients
  • Laboratory Evaluation
  • Imaging Evaluation
  • Obtaining Tissue Diagnosis
management of solitary pulmonary nodules
Management of Solitary Pulmonary nodules
  • A significant number of lung cancers are initially detected as asymptomatic radiographic abnormalities.
  • A solitary pulmonary nodule is defined as an asymptomatic mass within the lung parenchyma that is less than 3cm and is well circumscribed.
  • Overall 33% of these masses are malignant, and 50% are malignant if the patient is older than 50.
management of solitary pulmonary nodules26
Management of Solitary Pulmonary nodules
  • Discovery of a new nodule on chest film should begin with the review of previous chest radiographs.
  • Lesions that are new or increasing in size should be treated as pulmonary malignancies.
management of solitary pulmonary nodules27
Management of Solitary Pulmonary nodules
  • Fine needle aspiration should be performed
  • If FNA is positive then resection is recommended.
  • If the FNA is nondiagnostic, definitive treatment or other diagnostic measures should be undertaken.
  • A wedge resection of the nodule is not always possible and lobectomy may need to be utilized for both diagnosis and treatment
  • Mediastinal lymph node dissection should be performed as part of the definitive treatment.
conservative treatment in certain populations
Conservative treatment in certain populations
  • Patients with a mass unchanged for more than 2 years. Needs to be documented by serial radiography.
  • Patients with benign patterns of calcification such as hamartomas.
  • Patient with masses clearly caused by inflammatory causes.
symptomatic presentation of patients
Symptomatic Presentation of patients
  • Patients are usually 50-70 years of age.
  • Lung cancer is clinically silent for most of it’s course. The presentation of symptoms is associated with later-stage disease and a worse prognosis.
  • Most patients have bronchopulmonary symptoms: cough(75%), dyspnea(60%), chest pain(50%), and hemoptysis(30%).
signs and symptoms
Cough 75%

Weight loss 68%

Dyspnea 60%

Chest pain 50%

Sputum production 45%

Hemoptysis 30%

Malaise 26%

Bone pain 25%

Lymphadenopathy 23%

Fever 21%

Hepatomegaly 21%

Clubbing 20%

Neuropathy 10%

Superior Vena Cava 4% syndrome

Dizziness 4%

Hoarseness 3%

Asymptomatic 12%

Signs and Symptoms
symptomatic presentation of patients31
Symptomatic Presentation of patients
  • Other symptoms may include hoarseness, superior vena cava syndrome, chest wall pain, Horner syndrome, dysphagia, pleural effusion, or phrenic nerve paralysis.
  • Nonspecific symptoms such as anorexia, malaise, fatigue, and weight loss may occur in 70% of patients.
the silent killer
The Silent Killer
  • Because the pulmonary parenchyma does not contain nerve endings, many lung cancer grow to a large size before they cause local symptoms (hemoptysis, change in sputum production, dyspnea, obstruction, or pain).
cough
Cough
  • Either a new cough or a change in the nature of a chronic cough is the most common presenting symptom of bronchogenic carcinoma.
  • This symptom in a smoker should always cause concern.
hemoptysis
Hemoptysis
  • Hemoptysis, either gross or minor, commonly occurs when mucosal lesions ulcerate.
  • Although the most common cause of hemoptysis is bronchitis, this sign should always lead to further investigation.
obstruction
Obstruction
  • Tumors that obstruct major airways can produce wheezing, and unilateral wheezing suggests a localized obstruction
lung abscess
Lung Abscess
  • Lung cancer is often associated with cavitation and lung abscess formation, due either to airway obstruction with postobstructive pneumonia or to necrosis of a large tumor mass.
  • Clinical signs particularly indicative of malignancy associated lung abscess include chronicity of symptoms, lack of high fever, and lack of leukocytosis.
pleural effusions
Pleural Effusions
  • Pleural effusions occur in approx 10-20% of patients at the time of diagnosis.
  • It is the most frequent sign that a tumor is non-operable.
  • Invasion of the pericardium can lead to cardiac tamponade as well as arrhythmia.
superior vena cava syndrome
Superior Vena Cava Syndrome
  • Due to obstruction of the superior vena cava either by tumor or associated thrombosis.
  • Should be treated promptly following establishment of tissue diagnosis.
horner syndrome
Horner Syndrome
  • Results from involvement of the superior cervical ganglion.
  • Characterized by unilateral facial anhidrosis, ptosis, and miosis.
  • Hoarseness can occur from invasion of the recurrent laryngeal nerve either from the mass directly or by regional lymph nodes.
  • Hoarseness is most commonly assoc with unresectability.
pancoast syndrome
Pancoast Syndrome
  • Occurs in tumors involving the apex and superior sulcus of the lung.
  • Results from local invasion into the brachial plexus as well as the cervical sympathetic chain.
  • Clinical manifestations are dominated by shoulder and arm pain.
  • Can include Horner Syndrome and superior vena cava syndrome.
  • Delay in diagnosis is common due to the musculoskeletal component.
digital clubbing
Digital Clubbing
  • Digital clubbing is seen in a variety of pulmonary conditions but occurs most commonly in association with bronchogenic carcinoma.
other poor prognostic indicators
Other poor prognostic indicators
  • Esophageal obstruction
  • Vertebral body invasion
  • Distant extrathoracic tumor effects commonly involving lymph nodes, CNS, liver, bone and bone marrow, and the adrenal glands
paraneoplastic syndromes
Paraneoplastic Syndromes
  • Occur in 10% of patients with bronchogenic carcinoma.
  • Can be divided into systemic, endocrine, neurologic, cutaneous, hematologic, and renal categories.
endocrine abnormalities
Endocrine Abnormalities
  • Are relatively common in lung cancer.
  • Hypercalcemia is most commonly assoc with squamous cell and may occur directly due to bone invasion or indirectly due to Parathyroid Hormone.
  • SIADH and Cushing syndrome can be associated with small cell.
  • Elevations in ACTH may be found in 30-50% of small cell carcinomas.
  • Cushing syndrome is manifested by muscle weakness, hypokalemia, metabolic alkalosis, and diabetes.
neurologic disorders
Neurologic disorders
  • There is an association between small cell lung cancer and the Eaton-Lambert Myasthetic syndrome.
  • This syndrome is characterized by proximal muscle weakness, decreased or absent deep tendon reflexes, paresthesias, and autonomic dysfunction.
laboratory evaluation
Laboratory Evaluation
  • CBC
  • Electrolyte panel
  • Liver function tests
  • Serum calcium assay
  • Tumor Markers
tumor markers
Tumor Markers
  • Carcinoembryonic antigen (CEA)
  • Creatine Kinase BB (CK-BB)
  • Neuron-specific enolase (NSE)
  • Bombesin/gastrin-releasing peptide (GRP)
  • Tissue Polypeptide antigen (TPA)
  • CA-125
  • NSE and CEA are the markers used most frequently.
imaging evaluation
Imaging Evaluation
  • Chest X-ray
  • Computed Tomography
  • Magnetic Resonance Imaging
  • Positron Emission Tomography
  • Bone Scan
imaging evaluation49
Imaging Evaluation
  • Radiologic evaluation is an integral part of the diagnosis and treatment of lung cancer.
  • Chest radiography and CT of the chest and upper abdomen to assess Liver and adrenals are the standard for initial imaging.
  • Bone scan and MRI of the brain are reserved for organ specific or nonspecific symptoms.
imaging evaluation50
Imaging Evaluation
  • CT and MRI can identify the location of the primary tumor with respect to the other mediastinal structures.
  • However, it is difficult to determine if the mass merely abuts adjacent structures or if it invades them.
  • Often this distinction can only be made at the time of surgical exploration.
chest x ray
Chest X-ray
  • Chest films provide information regarding the size, shape, density, and location of the tumor.
  • Can also evaluate for the presence of thoracic lymphadenopathy, pleural effusion, pulmonary infiltrates, pneumonia, or consolidation.
  • Changes in the contour of the mediastinum secondary to lymphadenopathy, and mets to ribs or other bony structures may also be visualized.
chest x ray52
Chest X-ray
  • Most asymptomatic lung cancers are detected on chest radiographs.
  • Lesions smaller than 5-6mm are rarely noticed.
  • The radiographic appearance of a lesion cannot reliably distinguish between a benign and malignant process.
radiographic appearances characteristic of malignant lesions
Radiographic appearances characteristic of malignant lesions
  • Lobulation
  • Shaggy margins
  • Poorly defined margins
  • Calcifications (Concentric, Popcorn pattern)
ct scan
CT scan
  • CT scan of the chest reveals small nodules undetectable on routine chest X-ray.
  • CT provides more detail than chest X-ray regarding the surface characteristics of the tumor, relationships of the tumor to the mediastinum and mediastinal structures, and mets to lung, bone, liver, and adrenals.
ct scan58
CT scan
  • CT of the chest has a 65% specificity and an 85% sensitivity for identifying mediastinal lymphadenopathy.
  • When lymph nodes are greater than 1.5 cm in diameter, CT in approx 85% specific in identifying mets to mediastinal lymph nodes.
ct scan59
CT scan
  • CT scan for lung cancer should include the abdomen for evaluation of the liver, adrenals, and kidneys for metastasis.
slide62
MRI
  • MRI is helpful for evaluating apical lung lesions where the coronal reconstruction may be help to identify proximity to the brachiocephalic vessels and the brachial plexus and the spine.
  • MRI is particularly useful to detect vertebral, spinal cord, and mediastinal invasion in selected patients.
pet scan
PET scan
  • Cancer cells metabolize glucose more rapidly than normal cells.
  • The 18-fluorodeoxyglucose (FDG) given intravenously is trapped within malignant cells and can be imaged with PET
pet scan65
PET scan
  • PET scanning can often discriminate between benign and malignant parenchymal nodules.
  • The sensitivity and specificity of PET with FDG for detecting nonmalignant lesions ranges form 94-97% for benign lesions and 80-100% for malignant lesions.
  • Active inflammation may yield false results.
  • Carcinoid tumors as well as bronchioalveolar tumors take up the radiolabeled glucose poorly, leading to false negative scans.
tissue diagnosis
Tissue Diagnosis
  • The definitive diagnosis of lung cancer requires histopathologic or cytologic confirmation.
  • Methods for obtaining tissue include bronchoscopy, transthoracic needle aspiration, mediastinoscopy, thoracoscopy.
tissue diagnosis69
Tissue Diagnosis
  • Sputum cytology is positive in more than 50% of cases, especially in centrally located tumors.
  • Results of sputum samples are highly variable and interpretation my be difficult due to poor samples, purulence, malignant cell degeneration, poor sample preparation, and inexperienced cytologists.
tissue diagnosis70
Tissue Diagnosis
  • Negative sputum cytology in a suspicious setting should not be the basis for ending the evaluation.
  • Needle biopsy of suspicious pulmonary masses under either fluoroscopic of CT guidance is highly accurate, with a sensitivity of 90-95%
bronchoscopy
Bronchoscopy
  • For endoscopically visible lesions, bronchoscopy is diagnostic in over 90% of cases.
  • The sensitivity for peripheral lesions is lower than for directly visualized airway lesions.
  • Transbronchial biopsy may be performed with a special 21-gauge needle through the bronchoscope.
bronchoscopy72
Bronchoscopy
  • Bronchoscopy is recommended before any planned pulmonary resection if the sputum is positive with a negative chest X-ray or if atelectasis or an infiltrate fail to clear with medical management.
  • The surgeon always performs bronchoscopy to independently assess the endobronchial anatomy, exclude other tumors, and ensure all known cancer will be encompassed by the planned pulmonary resection.
mediastinoscopy
Mediastinoscopy
  • Cervical mediastinoscopy with sampling of lymph nodes is also highly accurate in selected patients with lymphadenopathy.
  • A mediastinoscopy should be a part of the evaluation in all patients with clinically suspicious lymph nodes on CT.
  • Lymph nodes > 1.5 cm are more likely to involved with metastasis from lung cancer.
mediastinoscopy75
Mediastinoscopy
  • Complications of mediastinoscopy are infrequent but include massive hemorrhage, injury to the trachea or bronchi, esophageal injury, and pneumothorax.
slide76
VATS
  • Video assisted thoracic surgery can evaluate enlarged aortic and inferior mediastinal lymph nodes
nsclc staging
NSCLC Staging
  • The most widely accepted system of staging for NSCLC is the TNM anatomic classification.
  • Stage I and II tumors are completely contained within the lung and may completely be resected with surgery.
  • Stage IV disease includes metastatic disease and is not typically treated by surgery except in those requiring surgical palliation.
nsclc staging78
NSCLC Staging
  • Stage IIIA and IIIB are locally advanced tumors with mets to the ipsilateral mediastinal structures or involving the mediastinal structures.
  • These tumors may be mechanically removed with surgery, however, surgery does not control the micromets.
sclc staging
SCLC Staging
  • Small cell carcinoma is not generally included in the TNM classification system.
  • The majority of small cell tumors are systemic at the time of diagnosis.
  • The two-stage system devised by the Veterans administration lung cancer study group is used for small cell staging.
  • The two-stage system classifies small cell as either limited or extensive.
management
Management
  • Options include
    • Surgery for localized disease
    • Chemotherapy for metastatic disease
    • Radiation for local control in patients not amenable to surgery
      • Radiation and chemotherapy together are better than either one alone for primary treatment of advanced cancer.
management82
Management
  • The most important prognostic factors identified to date are disease stage, performance status, and extent of weight loss.
  • Patients who have lost 5% or more of body weight in the preceding 2-6 months have a poor prognosis.
treatment of nsclc
Treatment of NSCLC
  • Stage I and II
    • Surgical resection is the treatment of choice in early stage lung cancer.
    • Wedge and segmental resections are safer but lead to a higher incidence of recurrence than pneumonectomy or lobectomy
    • 5 year survival rates for stage I and II disease are 60-70% and 40-55% respectively.
treatment of nsclc84
Treatment of NSCLC
  • Stage IIIA
    • Stage IIIA is included chest wall invasion, mediastinal nodal disease, and direct invasion of mediastinal structures.
    • IIIA is potentially resectable
    • 5 year survival rates are up to 40% with surgery
    • Unfavorable factors include gross extranodal disease and multiple nodal level involvement.
    • Studies indicate increased survival with either chemo or a combination of chemo and radiation before surgery.
treatment of nsclc85
Treatment of NSCLC
  • Stage IIIB
    • Patients with IIIB disease are generally unresectable.
    • Treatment with chemotherapy and/or radiation without surgery may improve survival rates.
treatment of nsclc86
Treatment of NSCLC
  • Stage IV
    • Disseminated disease occurs in the majority of patients with lung cancer.
    • At the time of presentation two thirds of patients already have disseminated disease.
    • Median survival time of 4 months
    • 1 year survival rate of approx 10-15%
    • Palliative treatment is the main option for the majority of these patients.
treatment of small cell
Treatment of Small Cell
  • Small cell cancer is assumed to be a systemic disease at the time of presentation.
  • Systemic chemotherapy is the treatment modality most commonly employed in these patients.
  • Combined chemo and radiation is the accepted standard of care for limited stage SCLC.
  • Surgery should only be considered for resection of solitary pulmonary nodules and must be followed by adjuvant chemotherapy.
novel therapies
Novel Therapies
  • Laser therapy
      • Useful for palliation of patients with obstructing disease
      • Nd-YAG is the most common type
  • Brachytherapy
      • Useful for palliation of patients with obstructing disease
      • Involves the placement of an ionizing radioactive source into the airway through catheters placed adjacent to the tumor.
novel therapies93
Novel Therapies
  • Photodynamic therapy
      • Involves the injection and subsequent uptake and selective retention of a hematoporphyrin derivative into the tumor cells
      • The compound is then photoactivated by light at 630nm to cause cell death.
      • Patients with localized stage I endobronchial lesions.
      • The majority of patients have a complete response of the tumor.