Pulmonary Neoplasms Flashcards
How many mutations are induced for every 15 cigarettes smoked?
one
RISK FACTORS FOR LUNG CANCER
7
- Smoking and second-hand smoke
- Asbestos – mesothelioma
- Radon – uranium mining
- Can develop lung cancer even after stopping smoking years ago
- Other family members who have had smoking-related cancers
- Prior lung diseases such as
- chronic bronchitis,
- emphysema, and
- tuberculosis - Air pollution:
Cigarette smokers have risk related to what factors of smoking?
5
- Age at onset of smoking
- Amount smoked
- Gender (women)
- Product smoked
- Depth of inhalation
Stopping tobacco use before middle age avoids more than ____of the lung cancer risk attributable to tobacco.
90%
We can treat smoking cessation with what drugs?
5
- Zyban (buproprion),
- Chantix (varenicline) or
- nicotine replacement therapy
- Clonidine and nortriptyline are recommended as second- line treatments
- hypnosis can work for some motivated smokers
What is a neoplasm?
What are the two kinds?
Neoplasia is uncontrolled cell growth
Growth that is not needed for normal development or replacement of dead or damaged tissues
Can be benign or malignant
What are the types of benign neoplasms?
Malignant? (two kinds)
Benign neoplasms – tumors
Hamartomas and granulomas
Malignant neoplasms– cancers
Metastatic
Primary: Bronchogenic carcinomas and others
small cell and non-small cell
What are the kind of metastatic neoplasms? 4
Primary?
breast, colon, prostate, bladder
Bronchogenic carcinomas and others small cell and non-small cell
BENIGN PULMONARY NEOPLASMS:
How do the cells grow? 3
Describe the borders? 2
Cells grow in fairly
- orderly manner,
- stick together,
- don’t migrate
Seem to be
- encapsulated,
- smooth borders
What are hamartomas?
What is often associated with these? 2
local tissues growing in disorganized manner
Often have
- bronchial tissue and
- calcifications (popcorn calcification)
What are granulomas?
Examples? 4
chronic inflammatory lesions with macrophages
- Tuberculosis
- Sarcoidosis
- Histoplasmosis
- Cryptococcosis
(homogeneous calcification)
MALIGNANT CELLS/TUMORS
- Describe the rate of cell division?
- What do they look like?
- How do the cells function? 2
- How do the masses themselves look?
- Rapid, even continuous division (occasionally in hours)
Cells are geared up for dividing - Show de-differentiation
Look less and less like parent cells or tissues - Lose some or all of their normal cell functions
Have no useful function for the body
Parasitize the host’s body
Steal nutrients, energy, blood supply – space occupying masses - Masses have irregular, invasive borders
Will travel in search of new lands to conquer
What are the different routes of spread for metastatic lung cancer?
4
Transcoelomic
Lymphatic
Hematogenous
Iatrogenic
Define the following routes of spread: Transcoelomic Lymphatic Hematogenous Iatrogenic
Transcoelomic: along the surface of an organ - mesothelioma
Lymphatic: most common route for carcinomas
Hematogenous: most common route for sarcomas
Iatrogenic: transplantation or implantation
What are the other most common places for cancer caused by smoking besides the lungs?
4
breast, colon, prostate, bladder
What is the most common type of lung cancer?
There are two types of this cancer. What are they? 2
BRONCHOGENIC CARCINOMA
- Small cell lung cancer – primitive neuroendocrine cells
- Non-small cell lung cancer
What are the types of non-small cell lung cancer?
3
- Adenocarcinoma
- Broncheoalveolar carcinoma (subtype of adenocarcinoma)
- Squamous cell carcinoma of the lung
- Large cell lung carcinoma
Name some other types of lung cancers?
5
- Carcinoid,
- Kaposi’s sarcoma,
- melanoma,
- lymphoma,
- head and neck
Mesothelioma
These four histologies account for approximately 90% of all epithelial lung cancers.
- Small Cell Lung Cancer (SCLC)
- Adenocarcinoma
- Squamous Cell Carcinoma
- Large Cell Carcinoma
SMALL CELL LUNG CARCINOMA
- Also known as what?
- What does it arise from?
- This is what percent of patients with lung cancer?
- Prognosis?
- 90% of pts with SCLC develop what?
- Also known as “oat cell” lung cancer
- Arises from primitive, small
neuroendocrine calls - 14% of patients with lung cancer
- Bad disease, early metastases
- Very aggressive cancer, rapidly fatal
- Only a small percentage of patients are curable
- Even with limited stage disease
- 90% of patients with SCLS develop brain metastases
Describe the tumor in small cell carcinomas.
2
- Poorly differentiated neuroendocrine tumor.
2. Central mass with endobronchial growth.
What might a SCLC produce?
4
What are these associated with?
May produce specific peptide hormones such as:
- adrenocorticotrophic hormone (ACTH),
- argininevasopressin (AVP),
- atrial natriuretic factor (ANF), and
- gastrin-releasing peptide (GRP).
These hormones may be associated with distinctive
paraneoplastic syndromes
Differential diagnosis for SCLC?
5
- Poorly differentiated non-small cell carcinomas
- Neuroendocrine carcinomas,
poorly differentiated squamous cell carcinoma - Nonepithelial tumors lymphoma,
- small round blue cell tumors,
- sarcomas (e.g., synovial sarcoma).
- Among women and young adults (less than 60 years), ____________ tends also to be the most common form of lung cancer.
- In lifetime never smokers, all histologic forms of lung cancer can be found, although ___________ tends to predominate.
- The incidence of small cell carcinoma is also on the ______.
- adenocarcinoma
- adenocarcinoma
- decline
NON-SMALL CELL LUNG CARCINOMA
- Is what percent of lung cancer?
- What are the three most common kinds?
- What do they have in common (2) and what makes them different (2) from each other?
- What are signs and symtpoms related to?
- What makes bronchoalveolar carcinomas different?
- 80% of lung cancers. Rare before age 35, peaks at 65-80
- NSCLC
- Adenocarcinoma of the lung 54%
- Squamous cell carcinoma of the lung 35%
- Large cell lung carcinoma 11% - All have similar prognosis and are treated the same, but have different locations and patterns of spread
- Signs/symptoms are related to the location of the tumor, may have associated paraneoplastic syndromes.
- Bronchoalveolar carcinoma is different, more aggressive
Subcategory of adenocarcinoma, found more peripherally
NSCLC - ADENOCARCINOMA
- Where does this cancer arise from?
- Found near which structures often? 3
- What may you see before primary symtpoms?
- What two findings will you find on tissue biopsy?
Associated with smoking
- Peripheral - arise from surface epithelium, peripheral scars
- Gland formation, papillary structures or mucin production
- May see metastatic disease before primary symptoms
- Hypertrophic osteoarthropathy and Trousseau’s syndrome
Adenocarcinomas…..take home?????
3
Peripheral lung locations.
Associated with a history of smoking.
It is the most common type of lung cancer occurring in never smokers
NSCLC: BRONCHOALVEOLAR ADNEOCARCINOMA is a subtype of adenocarcimona. How can it present?
It can occcur as early as when?
Can present as solitary or multicentric nodules, rapidly progressive
Can occur in 2nd decade of life – multiple pulmonary nodules
NSCLC: BRONCHOALVEOLAR ADNEOCARCINOMA
- Symtpoms present as?
- Nodal enlargement?
- Spread?
- Tends to occur is what tissues?
- Grows where?
- How can it present radiographically? 3
- How can it present on CT scans?
- Non-resolving focal or bilateral “pneumonia”
- Nodal enlargement uncommon
- Distant spread uncommon
- Tends to be more peripheral
- grows along the alveoli without invasion.
- present radiographically as a
- single mass, as a
- diffuse multinodular lesion, as a -fluffy infiltrate. - on CT scans as a “ground-glass” opacity (GGO).
Also seen in nonsmokers
NSCLC – SQUAMOUS CELL CARCINOMA
- What are the two kinds?
- Most frequently seen where?
- Tends to obstruct what?
- Describe its spread.
- CT sacn appearance?
- Squamous cell or epidermoid carcinoma
- Most frequently see in the proximal bronchi
- Tend to obstruct bronchi….. atelectasis or pneumonia
- Tend to remain localized and cavitate – Metastasize late.
- On CT Scans as a “ground glass” opacity
Lung Squamous Cell Carcinomas look like what compared to extrapulmonary types?
Where are they seen most?
What does the pattern look like? 3
- Identical to extrapulmonary (i.e., head and neck) squamous cell carcinomas .
- Occur centrally
Pattern is that of an
- infiltrating nest of tumor cells with
- central necrosis,
- resulting in cavitation.
NSCLC: LARGE CELL CARCINOMA. Least common subtype of NSCLC – 11%
Describe how the cells look?
How do we diagnose this?
How does the mass look? 2
- Large poorly differentiated cells
- Diagnosis of exclusion
- Large peripheral mass with
- prominent necrosis
Large Cell carcinomas
- Where are they seen mostly?
- Differentiated how?
- How do the cells look? 2
- How is the tumor arranged cell wise?
- occur peripherally.
- poorly differentiated carcinomas
- sheets of large malignant cells, often with
associated necrosis. - Cytologically, the tumor is also arranged in
syncytial (multinucleate mass of cytoplasm that is not separated into cells) groups and single cells.
CLINICAL PRESENTATION OF LUNG CANCER.
- May be asymptomatic with normal physical exam
- Symtpoms of centrally located lesions
- Symtpoms of peripheral lesions
- Symtpoms of metastases
What are symtpoms of the following:
- Symtpoms of centrally located lesions 7
- Symtpoms of peripheral lesions 1
- Symtpoms of metastases 4
Centrally located lesions:
- Cough,
- hemoptysis,
- wheezing,
- stridor,
- shortness of breath
- Collapse of lung due to tumor within or against the bronchus
- Post obstructive pneumonia
Peripheral lesions
1. Pain due to pleural or chest wall invasion
With metastases present
- Bone pain, back pain
- Difficulty breathing, chest wall pain
- Headache, seizures, and speech difficulties
- Weakness, weight loss, and loss of appetite
What kind of cancer should we think about when pneumonia isnt responding to treatment?
Think of bronchogenic CA when pneumonia not responding to treatment
Symtopms of lung cancer from most common to least common:
12
- cough
- weight loss
- dyspnea
- chest pain
- hemoptysis
- bone pain
- clubbing
- fever
- weakness
- SVCO
- dysphagia
- wheezing and stridor
LUNG CANCERS KILL THEIR HOST BY SPREADING THROUGHOUT THE BODY. What kinds of spread? 2
- LOCAL SPREAD IN CHEST IS THRU LYMPHATICS OR SIMPLE INVASION
- DISTAL SPREAD IS VIA BLOOD-HEMATOGENOUS
Lung Cancer-Metastasis. Where does it most commonly metastasis (startiing with the most common)? 4
Adrenals -50% of cancers
Liver – 30-50%
Brain – 20%
Bone – 20%
Clinical findings suggestive of metastatic disease:
Symtpoms elicited in history? 3
Signs found on physical examination? 8
Rountine laboratory tests? 5
- weight loss more than 10 lbs
- focal skeletal pain
- headache, syncope, seizures, extremity weakness
- lymphadenopathy
- Hoarseness
- superior vena cava syndrome
- bone tenderness
- hepatomegaly
- focal neurologic signs
- papilledema
- soft tissue mass
- Hematocrit less than 40% in men, less than 35% in women
- Elevated alkaline phosphatase
- GGT
- SGOT
- calcium levels
SYMPTOMS/SYNDROMES DUE TOREGIONAL METASTASES/INVASION
- Esophageal compression ….
- Laryngeal nerve paralysis ….
- Lymphatic obstruction ….
- Pericardial/cardiac extension …. 2
- Sympathetic nerve paralysis ….
- Cervical/thoracic nerve invasion ….
- Vascular obstruction ….
- dysphagia
- hoarseness
- pleural effusion
- effusion, tamponade
- Horner’s syndrome
- Pancoast syndrome
- SVC syndrome
- What is horner’s syndrome?
- What is this caused by? 2
- (involvement of what two areas?)
- How will it present? 3
- Lesion of superior cervical ganglion due to
- neoplastic or
- inflammatory involvement of
- cervical lymph nodes and
- proximal part of the brachial plexus
- Miosis (smaller pupil) and
- drooping of the eyelid with
- loss of sweating on that side of the face
PANCOAST’S SYNDROME is what?
(what nerves does it involve? 3)
How will it present?
Extension of tumor at apex of the lung involving C8, T1, T2
nerves and possible destruction of ribs
Shoulder pain radiating in the ulnar distribution
SUPERIOR VENA CAVA SYNDROME
90% of the time what is it due to?
How does it present? 4 types of symptoms
90% of the time due to bronchogenic cancer
- Swelling of face, neck, arms – venous dilation
- Shortness of breath, cough and chest pain suggesting
upper airway obstruction - Hoarseness, tongue swelling, nasal congestion
- Headaches, syncope, lethargy due to cerebral edema
What nerves are affected that cause hoarseness in SVCS?
3
- left vagus nerve
- Left recurrent nerve
- ligamentum arteriosum
PARANEOPLASTIC SYNDROMES
- Disease due to what?
- Mediated by what? 2
- May be the first sign of what?
- Whats the best treatment?
- Disease or symptom due to presence of cancer in the body
- Mediated by humoral factors (peptides) excreted by cancer cells
- May also be due to an immune response against the tumor
- May be the first manifestation of the cancer
Seen in 10% of patients with lung cancers - Best treatment is to treat the cancer
In paraneoplastic syndromes we treat the underlying cancer but we may also have to treat what?
2
May need to treat the metabolic changes as well
- -SIADH: Rx….vasopressin, fluid restriction, saline infusion
- -Cushing’s
PARANEOPLASTIC SYNDROMES signs and symtpoms?
3
- CACHEXIA
- HYPERCALCEMIA
- HYPERTROPHIC PULMONARY OSTEOARTHROPATHY
Describe the following in patients with PARANEOPLASTIC SYNDROMES:
- CACHEXIA
- Findings? 3 - HYPERCALCEMIA
- Most commonly seen with what kind of cancers?
- Two common findings? - HYPERTROPHIC PULMONARY OSTEOARTHROPATHY
- Common findings?
CACHEXIA - wasting syndrome
- Only syndrome that is common in NSCLC
- Weight loss,
- weakness,
- impaired immune function
HYPERCALCEMIA
- Most commonly seen with squamous cell cancer
- Bone metastases
- Ectopic production of a parathyroid hormone-like peptide
HYPERTROPHIC PULMONARY OSTEOARTHROPATHY
- Arthropathy and periostitis of long bones
- Clubbing of fingers and toes
Skeletal manifestations of lung cancer? 3
CUTANEOUS MANIFESTATIONS of Lung cancer? 2
- Clubbing - 30% (usually NSCLCs)
- Hypertrophic primary osteoarthropathy - 1–10% (usually adenocarcinomas).
- Periostitis
- Dermatomyositis and
- Acanthosis nigricans
NEUROLOGIC MANIFESTATIONS of lung cancer?
6
- Myopathic syndromes - 1%
- Myasthenic Eaton-Lambert syndrome and retinal blindness (SCLC).
- Peripheral neuropathies
- Subacute cerebellar degeneration
- Cortical degeneration
- Polymyositis
HEMATOLOGIC MANIFESTATIONS of lung cancer? 4
RENAL MANIFESTATIONS of lung cancer? 2
- Migratory venous thrombophlebitis (Trousseau’s syndrome),
- Nonbacterial thrombotic (marantic) endocarditis with
arterial emboli, - Disseminated intravascular coagulation (DIC)
- Thrombotic disease complicating cancer is usually a poor prognostic sign.
- Nephrotic syndrome and
- Glomerulonephritis
What is EATON-LAMBERT SYNDROME?
Autoimmune response usually causing proximal muscle weakness, usually in lower extremities
- EATON-LAMBERT SYNDROME can occasionally also affect what?
- And rarely?
- What is frequently depressed?
- In contrast to patients with myasthenia gravis, strength
________ with serial effort. - Initial treatment?
- Occasional autonomic dysfunction
- Rarely….cranial nerve symptoms
- Frequently…. depressed deep tendon reflexes
- improves
- Chemotherapy
SCREENING FOR LUNG CANCER
- Who should we screen?
- Should we do routine xrays and why?
- For patients with history of significant smoking – not everyone
Patients with 30+ pack years even if they quit within the last 15 years - Routine x-rays are ineffective and not recommended
Even if supplemented with sputum cytology
No decrease in incidence or mortality
SCREENING FOR LUNG CANCER
- What imaging might be helpful?
- What is the most common finding during screening? (What is the risk with this?)
- What has more positive health benefits than screening?
- Annual low dose helical CT screening may be recommended
Slightly decreases mortality - Most common finding is a benign nodule
Need to warn patients beforehand
May lead to invasive testing - Quitting smoking has a more positive health effect than screening
What technology has emerged as a new tool for lung cancer screening?
What is a major challenge confronting advocates of CT screening?
Low-dose, noncontrast, thin-slice helical or spiral chest CT
high false-positive rate.
It appears that nodules of what size are usually cancerous and which are not?
- less than 5 mm are unlikely to be cancerous and
2. 5–10 mm in diameter are of uncertain significance.
WORKUP FOR SOLITARY PULMONARY NODULE
What do these most commonly turn out to be? 3
More likely to be benign if? 4
More likely to be malignant if? 5
If there is a Low probability of malignancy what should we do?
If there is a High probability of malignancy what should we do?
- Lung Ca –
- Metastatic Ca –
- Granuloma (most common)
- Younger patient,
- smooth edges,
- not growing,
- calcification, less than 5mm
- Older patient,
- smoker,
- growing,
- rough edges,
- > 5mm
Follow with serial CTs for at least 2 years
Get tissue/resect
The Solitary Pulmonary Nodule: A Systematic Approach
5 steps
- Surrounded by normal lung tissue?
- Associated with adenopathy or atelectasis?
- Lesions larger than 3cm are almost always malignant.
- Solitary pulmonary nodules must be 3cm or less in diameter.
- Prompt diagnosis and resection are usually advisable if nodule is concerning
MULTIPLE PULMONARY NODULES
1. May be malignant or benign. Which are usually malignant and which are benign?
- Benign causes? 4
- Malignant
- Describe the Pattern?
- Describe the Nodular appearance?
- Describe the Reticular appearance?
- Describe the Reticulonodular appearance?
1.
> 1 cm, usually malignant
What kind of infections can cause benign multiple pulmonary nodules?
4
- septic emboli,
- fungi,
- TB,
- parasites
DIAGNOSIS AND WORK-UP OF LUNG CANCER
History and Physical
- Diagnostic tests? 6
- Lab tests?2
- Could be primary or metastatic. How can we tell the difference? 2
- What do we need to know about the cancer?
- Chest x-rays
- CT scans (chest, upper abdomen, adrenals),
- PET scans,
- bone scans,
- MRIs
- PFTs for candidates for chemoradiation or surgery
- CBC, CMP (includes electrolytes, liver enzymes)
- Need tissue to make histologic diagnosis
–Bronchoscopy or fine needle biopsy – central v peripheral lesions
– Bronchial washings, sputum cytology, or thoracentesis - Need to know the extent of the cancer (stage). Local invasion and distal spread
What might the chest xray show on a lung cancer pt?
3
- may show nodule(s),
- widening of mediastinum,
- pneumonia
Bronchoscopy is good for what kind of lesions as far out as what?
Good for central lesions as far out as the secondary bronchi
What is a fine needle biopsy used for?
What kind of procedure and what kind fo needle?
Image guided study? With what (3)?
Risks? 2
Peripheral lesions. Diagnostic yield: 90-97%
Out-patient procedure. 22 gauge needle
Image guidance: fluoroscopy, CT, ultrasound
Pneumothorax (10-30%) Hemoptysis (30%)
Describe the TNM Classification for lung cancer. 3
T (Primary tumor…where and size)
N (Regional lymph nodes metastisis)
M (Distant metastasis)
Small cell lung cancer – 2 stages
Describe them.
- Limited: confined to a single hemi-thorax
2. Extensive: malignant pleural effusion or metastatic disease
No evidence of distant spread…. must evaluate the mediastinum. Why?
Mediastinoscopy may show spread into lymph nodes
If mediastinum normal on CT, mediastinoscopy controversial
What tools would we use to stage lung cancers?
5
- History and physical, chest xray
- CT scan of chest and upper abdomen (include adrenals)
- CBC and BMP that includes electrolytes and liver enzymes
- Evaluate bone pain or increased serum ca++ or alkaline phosphatase with x-rays and/or bone scans
- Brain imaging in the asymptomatic not cost-effective
On a bone scan what are bright spots? 2
On a liver scan what are the dark spots?
Bone scan: bright spots are either arthritis or metastases
Liver scan: dark spots are metastases
TREATMENT OF LUNG CANCER
Treatment depends on the stage and type of lung cancer
4
- Surgery; limited disease, resectable lesion
- Radiation therapy
- Chemotherapy 4 -6 cycles recommended
- Targeted therapy: chemotherapy and radiotherapy
When would we only do radation therapy?
mediastinum, node positive limited stage disease
Lung cancer is usually treated with a combinations of therapies
Radiotherapy should begin with ____ or _____ chemotherapy cycle
first or second
90% of patients will develop brain metastases. Can we prevent this?
Prophylactic cranial radiation recommended with good central response
Need to balance benefits with side effects
- What are we taking out in lung surgery?
- What is radation therapy?
- What does target therapy accomplish? (what two drugs are involved?)
- What does adjuvant therapy accomplish?
- SURGERY resection of tumor and nearby lymph nodes
For NSCLC, lobectomy is the most effective - RADIATION – high-energy x-rays to destroy cancer cells
Significant side effects. Radiation pneumonitis in 15% of patients
Get PFTs to be sure patient has sufficient pulmonary function - TARGETED – stops action of abnormal proteins that promote growth
- -Avastin prevents formation of new blood vessels
- -Tarceva helps in NSCLC - ADJUVANT treatment before/after surgery to dec. recurrence
May be chemo, radiation, or targeted
SURGERY TYPES FOR LUNG CANCER 2
How is the surgery accomplished?
Big surgery –
- lobectomy or
- pneumonectomy
Now: video-assisted
thorascopic surgery
Pre-0p H&P – full tumor work-up – PFTs
Describe the following stages of SCLC and how to treat them:
Limited stage?
Extensive stage?
Cranial Spread?
Limited stage – one area of the chest
4-6 cycles of chemotherapy
Simultaneous mediastinal radiotherapy
Extensive stage – intrathoracic and distal spread
Chemotherapy only
Radiation for pain bone metastases or SVC syndrome
Cranial spread – frequently seen
Prophylactic radiation recommend for those responding to RX
TREATMENT OF NSCLC
Describe the following stages of NSCLC and how to treat them?
Stage 1? 2
Stage 2? 2
Stage 3? 2
Stage 4? 1
- Stage 1 (60-80%) confined to the lung
- Surgical resection
- May supplement with radiation or chemotherapy - Stage 2 (25-50%) has spread to lymph nodes in the lung
- Resection of tumor and nearby lymph nodes
- Chemotherapy and occasionally radiation - Stage 3 (10-30%) has spread to mediastinal nodes
- -IIIA same side as tumor: radiation + chemo + ?? resection
- -IIIB wider spread in mediastinum: chemo + ? radiation - Stage 4 other lobes or distal metastases
- -Is treated with chemotherapy
BRONCHOGENIC
CARCINOMA
looks like what?
Looks like pneumonia
but won’t go away
