Barksy: Pulmonary Neoplasms

Question 1

What is the most common cancer found in the lung?

Answer 1

metastasis!

**from breast, colorectal, endometrial carcinomas or soft tissue and bone sarcomas and skin melanomas

**the pleura can also be a site of metastasis, especially from breast cancer and ovarian cancer (transcoelomic spread)

Question 2

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

Answer 2

mets are stage 4 vs stages 1-3 in primary lung cancer
dramatic difference in prognosis
dramatic difference in therapy

Question 3

How do you distinguish a metastasis in the lung from a primary lung cancer?

Answer 3

microscopic appearance
multiple vs solitary lesions (a single mass in the lung is most likely primary, multiple masses most likely mets)
presence of precursor lesions (met wouldn’t have a precursor)
organ specific immunocytochemistry (ex: thyroid transcription factor)
molecular profiling

Question 4

What has happened to the death rates from lung and bronchus cancer in males and females in recent years?

Answer 4

Rates of deaths from these cancers began increasing after WWI, then decreased around 1980

Question 5

Which type of cancer is most common in males? In females? Which type of cancer causes the greatest amount of deaths across both genders?

Answer 5

males: prostate
females: breast
both: lung!!!

**5 year survival is really low for lung cancer :(

Question 6

What are the main causes of human lung cancer?

Answer 6

chemical carcinogens

UV/other ionizing radiation

Question 7

How do chemical carcinogens cause cancer?

Answer 7

from 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 they occur in junk DNA, they can be harmless

Question 8

What happens to your risk of lung cancer if you stop smoking?

Answer 8

your risk will decline, although your risk will still be greater than that of a non-smoker

**whether you stop at age 30, 40, 50, etc there is some benefit in quitting smoking, but there is a greater benefit if you quit when you’re younger

Question 9

How does UV radiation cause cancer?

Answer 9

similar to chemical carcinogens - formation of DNA adducts

differs from chemical carcinogens, because it causes single and double stranded breaks!

Question 10

Top two leading causes of lung cancer?

Answer 10

1. smoking
2. radon (in soil)

• *there are certain hotspots in the US where radon levels are high
• *radon levels are measured in homes before sales

Question 11

Two major types of cancer genes

Answer 11

oncogenes

tumor suppressor genes

Question 12

One of the major cancer genes involved in lung cancer

Answer 12

HER1 (EGFR)

**over-activation of this pathway causes increased invasion, mets, survival, and decreased apoptosis

Question 13

Explain how dysfunction in EGFR can lead to cancer growth and invasion

Answer 13

In malignancies, you can get overexpression or dysregulation of EGFR, which can increase the signaling response and result in cell cycle progression –> cell proliferation –> decreased apoptotic response –> increased cellular survival –> increased invasiveness and metastasis

Question 14

One of the most commonly mutated genes seen in virtually all types of human cancers
Multiple complex functions involving antiproliferation and apoptosis

**this gene mutation can’t be targeted as easily in therapy as HER1

Answer 14

TP53

Question 15

What is one important function of TP53?

Answer 15

senses DNA damage and arrests cells in G1 to induce repair

**if DNA can’t be repaired, BAX and other apoptosis genes are induced

Question 16

What are the four anatomical divisions of lung cancer?

Answer 16

central
peripheral (near the pleura)
mid-zonal
pancoast (tumor of pulmonary apex, frequently infects the sympathetic ganglion chain - causes Horner’s syndrome)

Question 17

How would a central lung tumor present?

Answer 17

cough, chest pain, hemoptysis, sputum

• *right next to the mainstem bronchus
• *can be seen with bronchoscopy

Question 18

How would a mid-zonal lung tumor present?

Answer 18

chest pain

Question 19

How would a peripheral lung tumor present?

Answer 19

silent, picked up accidentally via imaging

**too far to produce cough or hemoptysis

Question 20

How would a pancoast lung tumor present?

Answer 20

Horner’s syndrome

**due to invasions of sympathetic ganglion and chain

Question 21

What are the two major types of lung cancer?

Answer 21

1. small cell carcinoma

2. non-small cell carcinoma

Question 22

What are three types of non-small cell lung carcinomas?

Answer 22

1. squamous cell carcinoma
2. large cell undifferentiated carcinoma
3. adenocarcinoma (invasive vs noninvasive)

Question 23

Small cell carcinoma of the lung is also known as (blank) carcinoma

Answer 23

oat cell

Question 24

Central and mid-zonal primary lung cancers are often called (blank)

Answer 24

bronchogenic carcinoma

**because they occur beside the bronchi

Question 25

At what age do people get bronchogenic cancer? What is the overall 5-year survival? What is the prognosis?

Answer 25

age 55-65 **leading cause of cancer death in men and women overall survival for 5 years only 14% 50% have mets at diagnosis, strongly linked with smoking

Question 26

How do you treat small cell carcinoma?

Answer 26

sensitive to chemo w/ or w/o radiation | usu surgery not useful

Question 27

How do you treat non-small cell carcinoma?

Answer 27

treat with surgery | doesn't respond well to chemo

Question 28

14-18% of all primary lung cancer small “oat” cells usually central infiltrate widely and metastasize early (70%) derived from neuroendocrine stem cells makes polypeptide hormones- paraneoplastic syndromes

Answer 28

small cell carcinoma

Question 29

What area of the lung do small cell carcinomas affect?

Answer 29

usu central bronchi

Question 30

What are some paraneoplastic syndromes that can occur along with SMALL CELL cancer due to illegitimate transcription of small molecules?

Answer 30

Cushing's disease SIADH neuromuscular syndromes **These tumors can produce molecules, for example, like ADH, which can lead to SIADH

Question 31

Usu affects central airway with obstruction Tends to cavitate like TB Tend to spread to LN’s early but later outside of thorax More common in men May be preceded by years of metaplasia-dysplasia-CIS well differentiated to poorly differentiated

Answer 31

squamous cell carcinoma

Question 32

What are two paraneoplastic syndromes that occur along with squamous cell carcinoma?

Answer 32

``` hypercalcemia (produces a PTH-like hormone) pulmonary osteoarthropathy (finger clubbing) ```

Question 33

Enlarged fingertips and loss of normal angle at nail bed

Answer 33

finger clubbing **can be seen in all lung cancers, mechanism unknown

Question 34

10-18% of primary lung cancer undifferentiated under light microscopy special studies may reveal some signs of differentiation poor prognosis and metastasize early

Answer 34

large cell carcinoma

Question 35

``` grow slowly but metastasize early K-RAS oncogene mutation in 30% younger (40’s), women and nonsmokers generally occurs peripherally can be associated with scars pneumonia-like pattern grow slowly but metastasize early ```

Answer 35

adenocarcinoma **this is now the most common type of lung cancer

Question 36

Form of adenocarcinoma in situ Usually arises peripherally & lines the alveolar spaces Can be multifocal and bilateral Can be diffuse and mimic pneumonia Can be associated with pre-existing pulmonary scar Can be mucinous and non-mucinous

Answer 36

Bronchioloalveolar lung cancer **many pts with this disease are not smokers

Question 37

List 3 differences between bronchioloalveolar lung cancer and adenocarcinoma

Answer 37

1. BAC are a form of adenocarcinoma in situ 2. adenocarcinoma implies invasion 3. frequently BACs are adjacent to adenocarcinoma areas

Question 38

What kinds of lung tumors have lepidic spread (like the scales of the butterfly wing)?

Answer 38

BAC adenocarcinomas **no invasion of pulmonary stroma

Question 39

Neuroendocrine tumor Derived from Kulchitsky cells neurosecretory granules- carcinoid syndrome rare most occur in main stem bronchi, removal easier 30% can be either atypical carcinoids or malignant carcinoids and metastasize to hilar lymph nodes and few to distant sites. These atypical or malignant lesions have more mitoses and areas of necrosis

Answer 39

carcinoid tumor **better to have a carcinoid tumor than an adenocarcinoma or any other more malignant cancer

Question 40

Where do carcinoid tumors usually occur?

Answer 40

in the main stem bronchi

Question 41

What cells are associated with carcinoid tumors?

Answer 41

Kulchitsky cells

Question 42

“Coin lesion” on X-ray and CT scan

Answer 42

Bronchial chondromas **these are benign, many cases that are picked up on imaging, turn out to be bronchial chondromas

Question 43

neoplastic disease of pleura associated with asbestos exposure (plaques) not associated with smoking long latency period encase the lungs, cause restrictive lung disease direct pushing invasion of thoracic structures metastases rare patterns: sarcomatoid, epithelial and biphasic (both

Answer 43

primary malignant mesothelioma

Question 44

Neoplastic disease of the pleura

Answer 44

mesothelioma

Question 45

What will you see histologically in mesothelioma?

Answer 45

sarcomatoid or epithelial pattern, or both

Question 46

What is the cause of malignant mesothelioma?

Answer 46

absestosis from asbestos exposure | iron laden asbestos molecules

Question 47

What is the precursor lesion for mesothelioma?

Answer 47

pleural fibrous plaques **just know that most lung cancers have precursor lesions bc they follow normal cancer progression

Question 48

What is the precursor lesion for carcinoid and small cell carcinoma?

Answer 48

Kulchitsky cell hyperplasia

Question 49

What is the precursor lesion for peripheral adenocarcinoma and BAC?

Answer 49

can arise from scars | adenomatous hyperplasia and atypical adenomatous hyperplasia

Question 50

List the steps in the progression of a normal lung to BAC (bronchioalveolar lung carcinoma)

Answer 50

1. normal lung w normal type II pneumocytes in alveolus 2. transformed type II pneumocytes in alveolus 3. group of transformed cells spread in lipedic manner 4. differentiated bronchioalveolar lung carcinoma

Question 51

What is staging?

Answer 51

Staging: TNM T: tumor size N: lymph node involvement of hilar and mediastinal nodes M: absence or presence of mets

Question 52

T/F: Historically, there has been a lack of personalized medicine in lung cancer. However, an evolving new molecular classification of lung cancer is causing a paradigm shift in individualized therapy.

Answer 52

True

Question 53

10% of non-small lung cancer has HER pathway activated pathologically. These cancers are dependent on this pathway being activated. Why is this important?

Answer 53

if you can detect mutations in tyrosine kinase domain of EGFR, you can target these tyrosine kinases with medical therapy

Question 54

Two genes that can be rearranged leading to lung cancer; these cancers are sensitive to crizotibin

Answer 54

ALK | ROS

Question 55

T/F: Patients with particular lung cancers involving tyrosine kinase alterations, including EGFR mutation/deletion, ALK rearrangement, and ROS rearrangement, can be targeted specifically with tyrosine kinase inhibitors

Answer 55

True!