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Respiratory/Musculoskeletal > P- Neoplastic Lung Disease > Flashcards

P- Neoplastic Lung Disease Flashcards

1
Q

What is the prognosis of patients with bronchogenic carcinoma?
Why?

A

5 year survival of about 15%.
The prognosis is so poor because it is often discovered late in the course of disease and there is inadequate screening for it

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2
Q

What are the cancer-associated genes identified in non-small cell carcinoma?

A

KRAS
EGFR
p53
p16INK4a

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3
Q

What are the cancer associated genes identified in small cell carcinoma?

A 
c-KIT
MYCN
p53
3p
RB
BCL2
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4
Q

90% of lung cancers occur in smokers. What are the cancers with the strongest association to smoking?

A
  1. small cell carcinoma (20-25x)
  2. squamous cell carcinoma (10-15x)
  3. adenocarcinoma and large cell (2-4x)
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5
Q

In addition to lung cancer, what other cancers have a high association with smoking?

A

mouth, pharynx, larynx, esophagus, pancreas, bladder

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6
Q

What type of lung cancer is most likely to occur in non-smokers and women?
What is the suspected cause?

A

Adenocarcinoma and they tend to have a mutated EGFR

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7
Q

What are the 4 major risk factors for lung cancer.

A
  1. smoking
  2. industrial hazards (radiation, asbestos, arsenic, vinyl chloride, chromium nickel)
  3. air pollution (radon, uranium miners)
  4. genetic factors (mutated EGFR, p450 mutations)
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8
Q

What are the centrally located lung cancers (adjacent to the large stem bronchus)?

A
  1. small cell carcinoma
  2. squamous cell carcinoma

(both strongly associated with smoking)

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9
Q

What are the peripheral tumor lung cancers (not related to large bronchus) ?

A
  1. adenocarcinoma
  2. large cell carcinoma

Moderate association with smoking

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10
Q

What are the 2 major categories of lung cancers based on histology?
Why is it important to make these distinctions?

A
  1. NSCLC (adenocarcinoma, large cell carcinoma, squamous cell carcinoma) - 80% of all lung cancers
  2. Small cell carcinoma - 20% of all lung cancers

The difference is in the treatment: NSCLC respond best to surgical resection where small cell carcinomas respond best to chemotherapy

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11
Q

What are the 3 major gene mutations associated with adenocarcinomas of the lung?
Which are associated with NON-SMOKERS?

A

KRAS (30%)
EGFR (20%) - asian women, non-smokers
ALK rearrangement (4-6%)- non-smokers, signet ring cells

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12
Q

Who is the typical person to present with squamous cell carcinoma? Where is the mass located?
What are the complications?

A

Older male smokers with a central (major bronchi) lung mass that undergoes central necrosis/cavitary lesions.

Causes obstruction –> atelectasis and infection

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13
Q

What is the pathogenesis of squamous cell carcinoma?

What are the 2 gene mutations associated with it?

A
  1. It is preceded for years by squamous metaplasia and dysplasia (goblet cell hyperplasia, basal cell hyperplasia)
  2. It transforms into carcinoma in situ
  3. :Loss of tumor suppressor gene on chromosome 3p is early in benign epithelium of smokers
  4. loss of p53
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14
Q

What are the characteristic findings of a squamous cell carcinoma in well-differentiated tumors?

A
  1. keratinization (squamous pearls)
  2. intercellular bridges
  3. tadpole cells
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15
Q

Where do squamous cell carcinomas tend to spread to?

A

hilar lymph nodes (but this occurs later)

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16
Q

Who is most likely to be diagnosed with lung adenocarcinoma?
What are the 2 characteristic features of the tumor?

A

Women and non-smokers
It is a malignant epithelial tumor with :
1. glandular differentiation
2. mucin production

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17
Q

What are the major diseases (not cancers) associated with tobacco use/abuse?

A
  1. bronchitis
  2. MI
  3. atherosclerosis
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18
Q

Describe the progression to adenocarcinoma.

What are the 2 genes frequently mutated? Which has the worse outcome?

A
  1. atypical adenomatous hyperplasia
  2. bronchioalveolar carcinoma (in situ)
  3. invasive carcinoma

Mutations and amplifications of:

  1. EGFR- non-smokers, women, Asians (treated with tyrosine kinase inhibitors - Gefitinib)
  2. KRAS- smokers (worse outcome)
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19
Q

Where are adenocarcinomas generally located in the lungs?
What are the pathologic features?
Generally speaking, what is the growth rate and how quickly do they metastasize?

A

They are peripherally located, small in size, and associated with a scar. It can be acinar, papillary or solid.

They have glandular differentiation and mucin production.

It grows more slowly than squamous cell carcinoma but metastasizes widely and early

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20
Q

What is bronchioalveolar carcinoma?
Where does it tend to be located in the lung?
What is the general size and appearance?
What does it look like histologically?

A

It is adenocarcinoma in situ and is 3cm or less in size.
It is peripheral in the lung and can be a single nodule or multiple nodules that coalesce to look like a pneumonia consolidation.

Histologically it grows along a monolayer without destroying alveolar architecture or invading the stroma. “butterflies on a branch” - lepidic spread.

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21
Q

What are the 2 main subtypes of bronchioalveolar carcinoma? Which is more amenable to surgical resection?

A
  1. nonmucinous- usually single nodule and amenable to surgical removal
  2. mucinous- spreads aerogenously forming satellite nodules. less likely cured by surgery
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22
Q

What is atypical adenomatous hyperplasia?

A

Pre-neoplastic lesion (<0.5cm) of type II pneumocyte proliferation with only slight cytologic atypia.
It looks like a thickened septa but the cells in general look normal.
It progresses to bronchioalveolar carcinoma and then adenocarcinoma.

23
Q

Who is likely to present with small cell carcinoma of the lung?
Where in the lung is the lesion located?
What genes are likely mutated and what cells cause the aberrant growth?

A

Smokers- highly aggressive central tumor that has rapid growth and metastasizes widely. NO surgical resection. Must try chemo.

P53 and RB genes are frequently mutated and the cancer is presumed to arise from neuroendocrine cells

24
Q

Where do small cell carcinomas spread?

A

hilar and mediastinal lymph nodes

25
Q

Describe the histology of small cell carcinoma.

A
  1. Small cells with scant cytoplasm
  2. “salt and pepper” chromatin
  3. inconspicuous nucleoli
  4. ***prominent nuclear molding (press against each other and shape each other)
  5. ***crush artifacts- big purple crushed streaks
  6. abundant necrosis/apoptosis/mitosis
  7. Azzopardi effect
26
Q

What is the Azzopardi effect? What type of lung cancer is it associated with?

A

It is when blood vessel walls take up blue staining H&E due to nuclear material from crushed tumor cells clinging to the vessel.

It is seen in small cell carcinoma

27
Q

What is large cell carcinoma?

A

Undifferentiated malignant epithelial cells that do NOT:

  • form glands, secrete mucin
  • have keratinization pearls or intercellular bridges
  • are not small cell

It is a label of exclusion.
Highly malignant, poor prognosis.

28
Q

Only 15% of cancers are discovered in early stages (I or II) but the ones that are can be cured by what 2 techniques?

A

Lobectomy, pneumonectomy

29
Q

In general ____________ and ______________ tend to remain localized longer and have a slightly better prognosis than _______________ cancers.

A

adenocarcinoma and squamous cell carcinoma have better prognosis than undifferentiated (large cell) carcinomas.

30
Q

What are the most often locations of spread of lung cancers that metastasize?

A
  1. ADRENALS ***
  2. liver
  3. brain
  4. bone
31
Q

In addition to cough, weight loss and dyspnea, what are the 3 less common but classic presentations for lung cancer?

A
  1. Vena Caval syndrome
  2. Horner’s syndrome
  3. Paraneoplastic syndrome
32
Q

What is vena caval syndrome?

A

Compression of the superior vena cava due to tumor in the lung that occludes blood return to the heart resulting in congestion and edema of the face, neck, and upper extremities

33
Q

What is Horner’s syndrome?

A

Pancoast tumor that can invade:

  1. brachial plexus– ulnar nerve pain
  2. cervical sympathetic chain- ptosis, anhydrosis, miosis (pinpoint eyes)
34
Q

What is a paraneoplastic syndrome?

A

Symptoms in cancer patients that cannot be attributed to local or distant spread of the tumor but rather are due to the production of hormones endogenous to the tissue from where the tumor came.

35
Q

What hormones are secreted as a paraneoplastic syndrome of small cell carcinoma? What does each cause?

A
  1. ADH- hyponatremia

2. ACTH- Cushing syndrome

36
Q

What hormones are secreted as a paraneoplastic syndrome of squamous cell carcinoma? What does it cause?

A

Parathyroid hormone related peptide (PTHrP) which causes hypercalcemia

37
Q

What are the 6 hormone or hormone-like factors secreted by lung cancer cells?

A
  1. ADH- hyponatremia
  2. ACTH- Cushings
  3. PTHrP - hypercalcemia
  4. calcitonin- hypocalcemia
  5. gonadotropin- gynecomastia
  6. serotonin and bradykinin- carcinoid syndrome
38
Q

In addition to hormone release, what other systemic manifestations are paraneoplastic syndromes associated with lung cancer?

A
  1. Lambert Eaton myasthenia
  2. peripheral neuropathy
  3. hypertrophic pulmonary osteoarthropathy (clubbing of fingers)
  4. acanthosis nigricans
  5. leukemoid reactions/thrombi
39
Q

Who do carcinoid tumors usually affect?
Where are they found in the lung?
What cells are carcinoid tumors composed of?

A

They affect younger non-smokers and are generally benign.
They form a central polyploid mass that projects into the lumen of the bronchus and are composed of neuroendocrine cells.

40
Q

What do carcinoid tumors look like in histology?

A

Nesting pattern - islands of tumor cells with regular round nucleus and moderate cytoplasm
Mitoses are rare and there is no necrosis
They form Rosettes and ribbon like patterns

41
Q

What is carcinoid syndrome?

A

A rare effect of carcinoid tumors that presents with:

  1. diarrhea
  2. flushing
  3. cyanosis
42
Q

What are the 3 steps of increasing aggressiveness of neuroendocrine neoplasms?

A
  1. typical carcinoid
  2. atypical carcinoid (faster mitotic rate, focal necrosis)
  3. small cell carcinoma
43
Q

What are the most common cancers that metastasize to the lungs?
How do they present differently from lung cancers?

A

Breast, colon, kidney, stomach, pancreas

Instead of single nodules, they are multiple nodules scattered in the parenchyma and more common in the periphery

44
Q

What are the 2 broad categories of effusion in the lungs? Which is more likely to be reabsorbed?
What is the likely cause of each?

A
  1. Transudate- watery and likely to reabsorb. CHF

2. Exudate- proteinaceous, fibrous, scarring, not likely to reabsorb (infection, cancer, pulm. infarct)

45
Q

What are the 2 major types of asbestos? Which is more oncogenic?

A
  1. serpentine- chrysophile- NOT oncogenic

2. amphibole- crocidolite- ONCONGENIC

46
Q

What are the 3 most common causes of mesothelioma?

A
  1. asbestos exposure
  2. radon (uranium exposure)
  3. SV40 virus–> T antigen inactivates p53 and RB
47
Q

What cells do mesothelioma arise from?

A

Parietal or visceral pluera (rarely peritoneum)

48
Q

How long is the latency period for asbestos related mesothelioma?

A

25-45 years

49
Q

What is the relationship between mesothelioma and smoking?

A

Smoking is NOT shown to increase the risk for mesothelioma but there is an increased risk of asbestos related bronchogenic lung cancer in smokers

50
Q

What is seen histologically in the LUNG tissue of someone with mesothelioma?

A

Asbestos bodies (chains of iron coating asbestos fibers)

51
Q

What part of the lung is affected by mesothelioma?

A

It causes diffuse lesions that spread in the pleural space, and interlobar regions.
It ensheaths the lung in thick fleshy tumor

52
Q

What are the two cytological types of mesothelioma?

A
  1. epithelioid
  2. spindle

Both can be found in the same tumor

53
Q

What bronchogenic cancer resembles mesothelioma in shape and distribution?
How do you differentiate between the two?

A

Adenocarcinoma is peripheral and can be glandular, papillary or tubular like mesothelioma.
Differentiate these two with:
1. immunohistochemical staining (adeno-CEA+ and mesothelioma calretinin+)
2. electron microscopy - spaghetti like microvilli on surface of mesothelial cells

54
Q

What is the prognosis for mesothelioma?

A

50% of patients die in 12 months and few survive longer than 2 years

Respiratory/Musculoskeletal (36 decks)

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