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Block 9 week 3 > Pulmnary neoplasms - Barsky > Flashcards

Pulmnary neoplasms - Barsky Flashcards

1
Q

Are the spleen and kidney common places for metastases?

A

No.

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2
Q

Are the lungs and liver common sites for metastatses?

A

Yes.

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3
Q

What is the most common site for metastases?

A

The lungs.

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4
Q

What is more common, primary lung cancer or metastases to the lung?

A

Metastases.

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5
Q

What is transoelomic spread?

A

When cancer travels to the lungs via the peritoneal and pleural surfaces.

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6
Q

Why is it important to distinguish between a metastasis and a primary lung cancer?

A

If the cancer is a met then it is already considered to be Stage 4 cancer. There is also a dramatic difference in the prognosis and therapy used to treat the two different types of cancer.

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7
Q

How can you distinguish between a met and primary lung cancer?

A
  1. microscopic appearance
  2. multiple vs. single lesion. Single lesion is more likely to be primary (but this is not always discriminatory).
  3. Presence of precursor lesions – more likely primary
  4. Organ specific immunocytochemistry – such as TTF-1
  5. Molecular profiling – look for markers
  6. On gross appearance – mets tend to be more round and globular
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8
Q

What is TTF-1?

A

Thyroid Transcription Factor-1. A marker specific for lung cells – Type 2 pneumocytes.

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9
Q

What is the most important risk factor for lung cancer?

A

Smoking.

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10
Q

What type of cancer is associated with the most deaths in both men and women?

A

Lung cancer.

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11
Q

What are the causes of cancer?

A
  1. environmental carcinogens – (ie. Smoking)
  2. UV radiation
  3. Other ionizing radiation – ie. radon
  4. Viruses
  5. Lifestyle, diet, immune status
  6. Hereditary factors or genes
  7. Unknown
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12
Q

What are the most important causes of lung cancer?

A

Environmental carcinogens such as smoking and UV radiation.

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13
Q

How do chemical carcinogens contribute to cancer?

A

Acts by forming DNA adducts which give rise to mutations. If mutations occur in hot spots, spots which change gene expression or protein, mutations can be carcinogenic. If mutations occur in introns or junk DNA or in the non coding strand they can be harmless.

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14
Q

What is the smoking threshold after which there is an increase in the risk for cancer?

A

10 pack years.

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15
Q

Smoking cessation at any age gives benefits but….?

A
  1. The longer the time smoking, the higher the risk – even after smoking cessation. This is due in part because the DNA adducts are still present.
  2. The younger the age of smoking cessation, the greater the benefit of quitting because DNA repair is more robust when we are younger.
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16
Q

How does UV radiation and other ionizing radiation contribute to cancer?

A
  1. action is similar to chemical carcinogens – formation of DNA adducts
  2. action is different to chemical carcinogens in that radiation causes single and double strand DNA breaks
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17
Q

Next to smoking, which is the second leading cause of lung cancer?

A

Radon exposure.

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18
Q

What are the five basic categories of oncogenes?

A
  1. growth factors
  2. growth factor receptors
  3. Signal transducing proteins
  4. nuclear transcription factors
  5. cyclins and cyclin dependent kinases
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19
Q

Cancer may be caused by oncogenes and also what?

A

Inactivation of anti-oncocenes such as:

  1. growth inhibitory factors
  2. molecules that regulate cell adhesion
  3. molecules that regulate signal transduction
  4. molecules which regulate nuclear transcription and cell cycle
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20
Q

What is the most important oncogene associated with lung cancer?

A

HER1 – also called EGFR or epidermal growth factor receptor. This receptor has a tyronsine kinase domain that is activated in lung cancer.

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21
Q

The HER family of receptors activates what pathway?

A

The MAPK pathway. This pathway triggers a signal cascade that leads to increased angiogenesis, increased cell proliferation, increased metastasis and increased ability for cancer cells to invade.

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22
Q

How is TP53 related to cancer?

A
  1. is one of the most commonly mutated genes in all types of cancer
  2. Has multiple, complex functions
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23
Q

What are some functions of TP53?

A
  1. senses DNA damage and arrests cell in G1 and induces DNA repair – increased CDK1 and p21 preventing phkosphorylation of RB which induces GADD45. GADD45 aids in DNA repair.
  2. if DNA cannot be repaired apoptosis genes such as BAX are induced
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24
Q

Can the HER1 receptor be targeted in lung cancer therapy?

A

Yes

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25
Q

Can the TP53 mutation be targeted in lung cancer therapy?

A

No. But it is a predictive marker that is associated with prognosis.

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26
Q

Where does central lung cancer arise?

A

Near the bronchi.

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27
Q

What are the types of primary lung cancer?

A
  1. Central – near bronchi
  2. Peripheral – near pleura
  3. Mid-zonal – in between central and peripheral
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28
Q

What is Pancoast lung cancer?

A

A type of peripheral lung cancer that arises in the apex of the lung. It invades the sympathetic ganglion.

29
Q

What are some symptoms associated with pan coast lung cancer?

A

Basically causes Horner’s syndrome because of invasion of the sympathetic ganglion and chain:

  1. constriction of pupil - miosis
  2. shrunken in eye - enophthalmos
  3. abnormal facial sweating - anhidrosis
  4. ptosis
30
Q

Describe the classic presentation with central lung cancer.

A
  1. can get obstruction and pneumonia in central cancers
  2. present with cough, chest pain, hemoptysis, sputum
  3. Bronchoscopy can be used for biopsy due to location
31
Q

Describe the classic presentation with peripheral lung cancers.

A
  1. often silent and asymptomatic
  2. picked up incidentally on chest X-ray or CT scan
  3. fine needle aspiration used for biopsy due to location
32
Q

What type of lung cancer is more common today?

A

Peripheral cancers. These tend to be adenocarcinomas that are associated with smoking of filtered cigarettes.

33
Q

What type of lung cancer is associated with smoking unfiltered cigarettes?

A

Central lung cancers which tend to be squamous cell cancers.

34
Q

What are the 2 major types of lung cancer?

A
  1. small cell carcinoma

2. non-small cell carcinoma

35
Q

What are the subtypes of non-small cell carcinoma?

A
  1. squamous cell carcinoma
  2. large cell undifferentiated carcinoma
  3. adenocarcinoma
36
Q

Adenocarcinoma is further categorized as….?

A
  1. invasive adenocarcinoma

2. non-invasive adenocarcinoma – such as bronchoalveolar carcinoma (BAC)

37
Q

What is another name for small cell carcinoma?

A

Oat cell carcinoma.

38
Q

Is size the only difference between small cell and non-small cell carcinomas?

A

No. Small cell carcinomas do have smaller cells (with smaller nuclei) but there are also many other differences and the therapy for the two is completely different.

39
Q

Central and mid-zonal primary lung cancers are often termed…?

A

Bronchiogenic cancer.

40
Q

What are some characteristics of bronchiogenic cancer?

A
  1. can be either small cell or non-small cell carcinoma
  2. can be squamous, adenocarcinoma or undifferentiated
  3. peaks around ages 55-65
  4. is the leading cause of cancer death in men and women
  5. overall 5-year survival is only 14%
  6. 50% have metastasis at diagnosis
  7. is strongly linked with smoking
41
Q

What is the treatment for small cell carcinoma?

A

Chemotherapy with or without radiation. This type not usually amenable to surgery.

42
Q

What is the treatment of non-small cell carcinoma?

A

Usually better treatment with surgery and respond poorly to chemotherapy.

43
Q

Describe some characteristics of small cell carcinomas.

A
  1. usually presents as a central cancer – near the central bronchi
  2. infiltrate widely and metastasize early - 70%
  3. derived from neuroendocrine stem cells
  4. can synthesize and release polypeptide hormones leading to presentation with a paraneoplastic syndrome
44
Q

What are some paraneoplastic syndromes?

A
  1. Hypercalcemia
  2. Cushing’s disease
  3. SIADH
  4. Neuromuscular syndromes
  5. Pulmonary osteoarthropathy or finger clubbing (is actually associated with all types of lung cancers)
45
Q

What are 3 neoplastic syndromes that are especially associated with small cell cancer?

A
  1. Cushing’s disease
  2. SIADH
  3. Neuromuscular syndromes
46
Q

Describe some characteristics of squamous cell carcinoma.

A
  1. can cause central airway obstruction
  2. well differentiated to undifferentiated
  3. tends to cavitate
  4. tends to spread to lymph nodes early and tends to spread outside of the thorax later
  5. more common in men
  6. associated paraneoplastic syndromes include – hypercalcemia
  7. pulmonary osteoarthropathy
  8. may be preceded by years of metaplasia-dysplasia (carcinoma in situ)
47
Q

Finger clubbing is characterized by….?

A

Enlarged fingertips and loss of the normal angle at the nail bed.

48
Q

Describe some characteristics of large cell carcinoma.

A
  1. undifferentiated under light microscopy
  2. special studies may reveal some signs of differentiation
  3. poor prognosis and metastasize early
49
Q

Adenocarcinomas………..?

A

Grow slowly
Metastasize early
Are associated with K-RAS defect 30% of cases
Tend to occur in younger women and non-smokers
Are generally peripheral cancers that may be associated with scars and are pneumonia like
AH and AAH are precursor lesion

50
Q

Describe bronchioalveolar lung cancer (BAC).

A
  1. usually arises peripherally
  2. can be multifocal and bilateral
  3. can be diffuse and mimic pneumonia
  4. can be associated with a pre-existing scar
  5. can be mucinous and non-mucinous
  6. is a subtype of adenocarcinoma and is sometimes called adenocarcinoma in situ because it lines the alveolar spaces instead of infiltrating them
  7. AH and AAH are precursor lesions
51
Q

Adenocarcinoma’s are different from BAC how?

A

Adenocarcinoma’s are invasive while BAC is a form of adenocarcinoma in situ.
BAC areas are often found adjacent to adenocarcinoma areas.

52
Q

What is lepidic spread?

A

Spread or proliferation along the septae – there is no invasion of the pulmonary stroma.

53
Q

What are carcinoid tumors?

A
  1. low-grade tumors that tend to occur in central airways – especially main stem bronchi (removal is easier)
  2. can have neuroendocrine differentiation – associated with Kulchitsky cells which are filled with neurosecretory granules
  3. are rare
  4. can be malignant- this form resembles small cell cancer, can metastasize to hilar lymph nodes and to a few distant sites. This type has lesions with more mitoses and areas of necrosis
54
Q

Describe bronchial chondromas.

A
  1. also called ‘coin lesions’ due to appearance on X-ray and CT scan
  2. are benign
55
Q

What is neoplastic disease of the pleura?

A
  1. can be due to metastases – secondary cancer

2. can be primary – called malignant mesothelioma

56
Q

Describe malignant mesothelioma.

A
  1. associated with asbestos plaques from exposure (asbestiosis)
  2. not associated with smoking
  3. lung encased
  4. direct pushing invasion of thoracic structures
  5. metastases are rare
  6. patterns – sarcomatoid, epithelial and biphasic
  7. increases chance of lung cancer if have mesothelioma and smoke
57
Q

What are ferruginous bodies?

A

Plaques of asbestos that are crusted with iron. Seen in asbestosis.

58
Q

Most lung cancers have what?

A

Precursor lesions such as:

  1. squamous cell dysplasia or carcinoma in situ in the central bronchus
  2. adenomatous hyperplasia (AH) and atypical adenomatous hyperplasia (AAH) in the periphery
  3. pleural fibrous plaques for mesothelioma
  4. Kulchitsky cell hyperplasia for carcinoid and small cell carcinoma
59
Q

What is the TMN classification?

A
  1. used to stage cancer
  2. T = size of primary tumor
  3. M = are there metastases to distal sites
  4. N = is there nodal involvement and extent of this involvement
60
Q

What is the purpose of staging cancer?

A

It is used to determine prognosis and to guide therapy.

61
Q

What is ALK?

A

An oncogene that is associated with lung cancer.

62
Q

10% of non-small cell cancers, especially in non-smokers, have what?

A

EGFR tyrosine kinase molecular alterations.

63
Q

5% of non-small cell cancers, especially in non-smokers have what?

A

ALK rearrangements.

64
Q

3-5% of non-small cell cancers, especially in non-smokers have what?

A

ROS rearrangements.

65
Q

What are some ways that the HER receptor can be targeted in cancer therapy?

A
  1. HER dimerization inhibitors – ie. Trastuzumab
  2. Anti- EGFR blocking antibodies – ie. Cetuximab
  3. Antiligand blocking antibodies
  4. Tyrosine kinase inhibitors –ie. Erlotinib, Gefitinib, Iapatinib
  5. Ligand-toxin conjugates – TP-38, DAB, EGF, ETA fusion toxin
66
Q

EGFR activating mutations and/or deletions results in….?

A

Oncogene addiction.

67
Q

Explain oncogene addiction.

A
  1. either exons 19 (may be deleted) or 21 (L858R mutation leads to amino acid substitution at position 858. Leucine to an Arginine) are affected. These correspond to tyronsine kinase activity of EGFR
  2. The effected exons are either deleted or have a point mutation and the effect is either self activation or downsteam signaling
  3. The presence of either the deletion or the mutation makes the tumor sensitive to treatment with tyrosine kinase inhibitors
68
Q

Name two other molecular issues that can lead to cancer.

A
  1. ALK rearrangement
  2. ROS translocation
    Rearrangement leads to these genes being placed nex to other genes so that when that gene is activated so is the ROS or ALK. This leads to increased cancer cell survival, tumor growth, tumor cell proliferation.
69
Q

Tumor cells with ALK or ROS gene rearrangements are sensitive to what drug?

A

Crizotinib.

Block 9 week 3 (5 decks)

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