Lung Cancer Path and Phys

Question 1

Primary bronchogenic carcinomas are divided into these two categories. What are these categories based on, and what is the break up

Answer 1

1. Non-Small Cell Lung Carcinoma (75%)
2. Small Cell Lung Carcinoma (20%)

Based on their response to available surgery

NSCLC: surgery

SCLC: chemotherapy

Question 2

What are the 5 types of Non small cell carcinoma?

Answer 2

1. Sqamous Cell Carcinoma
2. Adenocarcinoma
3. Large Cell Carcinoma
4. Bronchioloalveolar carcinoma
5. Carcinoid

Question 3

Adenocarcinoma of the lung:

• characteristic histology
• association
• location

Answer 3

• glands or mucin, papillary pattern
• most common tumor in nonsmokers and female smokers
• peripheral

Question 4

lepidic growth pattern

Answer 4

usually seen in bronchioloalveolar carcinoma

• “butterflies sitting on a fence”
• grows along preexisting structure i.e. bronchioles, alveolar septa, without destroying alveolar architecture (no invasion)

Question 5

Sqamous cell carcinoma of the lung:

• characteristic histology
• association
• location
• comment

Answer 5

• keratin pearls or intercellular bridges (desmosomal connections between the cells)
• most common tumor in male smokers, usually see tumor suppressor Loss Of Function (LOF)
• central
• may produce PTHrP (hypercalcemia)

Question 6

large cell carcinoma of the lung

• characteristic histology
• association
• location
• comment

Answer 6

• poorly differentiated LARGE cells, anaplastic (NO kertain pearls, intercellular bridges, glands or mucin)
• smoking
• central OR peripheral (can be variants of squamous and adenoma)
• poor prognosis

Question 7

Small cell carcinoma of the lung

• characteristic histology
• assocation
• location
• comment

Answer 7

• poorly differentiated small cells; arises from neuroendocrine (Kulchitsky) cells
• male smokers
• central
• rapid growth and early metastasis; may produce ADH or **ACTH **or cause Eaton-Lambert syndrome (paraneoplastic syndrome)

Question 8

oat cells

Answer 8

small cells that characterize small cell carcinoma

• look like lymphocytes, uniform in shape and size, but theyre infact 2-3x larger in size
• hyperchromatic nuclei
• chromatin “salt and pepper” appearance
• scarce cytoplasm

Question 9

Clinical manifestations of:

Adenocarcinoma

What is the 5 year survival?

Answer 9

pleuritic chest pain (since peripheral), effusion, weight loss, dyspnea

5 year survival = 10%

Question 10

Clinical manifestations of:

Squamous cell carcinoma

What is the 5 year survival?

Answer 10

cough (since central), dyspnea, weight loss

5 year survival: 10%

Question 11

Clinical Manifestations of:

Small cell carcinoma

What is the 2 year survival?

Answer 11

paraneoplastic syndromes, cough, hemoptysis, weight loss, dyspnea

2 year survival = 25%

Question 12

In metatastases of lung cancer, no organ is spared, but the 4 major sites (and percentage of cases) are the following:

Which type of lung cancer characteristically involves the bone marrow?

Answer 12

“BLAB”

1. Brain (20%)
2. Liver (30-50%)
3. Adrenals (>50%)
4. Bone (20%)

Small cell lung carcinoma characteristically has widespread focal involvement of bone marrow

Question 13

diagnosis of lung cancer (5)

Answer 13

1) chest radiograph and CT scanning
2) sputum cytology and bronchial lavage
3) fiberoptic bronchoscopy
4) needle biopsy
5) molecular pathology, fluorescence bronchoscopy, endobronchial ultrasound, spiral computed tomogrpahy

Question 14

T4 (general meaning of status)

Answer 14

Tumor of any size invading mediastinum, heart, esophagus, trachea, etc.

Question 15

List 4 main carcinogens in tobacco smoke

Answer 15

1) polycyclic aromatic hydrocarbons: penzopyrene from tars
2) nitrosamines
3) aromatic amines
4) free radicas and nonradical oxidants

Question 16

5 major molecular pathways in the pathogenesis and progression of lung cancer

Answer 16

1) inactivation (or silencing) of tumor suppressor genes
2) activation of oncogenes
3) evasion of apoptosis
4) DNA repair defects
5) telomerase dysregulation

Question 17

List the changes in epithelium as it goes from early to intermediate to late stages

Answer 17

normal epithelium –> hyperplasia –> squamous metaplasia –> dysplasia (intermediate) –> carcinoma in situ (late) –> invasive carcinoma

Question 18

For each change in epithelium, list the molecular changes/markers observed:

Normal epithelium:

Hyperplasia:

Squamous metaplasia:

Dysplasia:

Carcinoma In situ/Invasive Carcinoma:

Answer 18

Normal epithelium: 3p21-9b21 LOH

Hyperplasia: telomerase inactivation

Squamous metaplasia: P15/NK4a methylation

Dysplasia: FHIT inactivation 8p22-24 LOH

Carcinoma In situ/Invasive Carcinoma: Tp53 inactivation, 5q22 LOH

Question 19

What are the major mutations/molecular pathology of lung adenocarcinoma? (5)

Answer 19

1. EGFR mutation
2. EML4-ALK rearrangements (anaplastic lymphoma kinase)
3. KRAS mutations (kirsten rat sarcoma viral oncogene)
4. MET amplifications (mesenchymal epithelial transition factor)
5. ROS-1

Question 20

What do all of the EGFR (HER/ERbB) have in common?

Answer 20

Tyrosine kinase domains on the opposite site of where the lingand binds (intracellular)

Question 21

5 effects of signaling pathway of EGFR

Answer 21

1. angiogenesis
2. differentiation
3. motility
4. proliferation
5. survival

Question 22

Current therapy for lung cancer (4)

Answer 22

1. Surgery
2. Radiation
3. Chemotherapy
4. Targeted therapy

Question 23

3 main NEW targeted therapies for lung cancer

Answer 23

1) EGFR family inhibitors
2) ALK tyrosine kinase inhibitors
3) immune checkpoints blockade

Question 24

5 less important new targeted therapies

Answer 24

1. inhibitors of angiogenesis
2. inhibitors of signal transduction
3. inducers of apoptosis
4. inhibitors of eicosanoid pathway
5. demethylating agents

Question 25

3 promising treatments for immune checkpoint blockade: * mAb anti-CTl-4 * mAb anti-PD-1 * mAb anti-PD-L1

Question 26

2 ways to create immunosuppressive microenvironment

Answer 26

1. production of immunosuppressive cytokines (TGF-B, IL-10, VEGF) * TGF-B normally inhibits the cell cycle 2) expression of co-inhibitory immune checkpoint molecules (CTLA-4, PD-1)

Question 27

3 most common sources (cancers) of osteoblastic metastases

Answer 27

1. small cell lung cancer 2. prostate gland carcinoma 3. breast carcinoma

Question 28

Molecular pathology of squamous cell carcinoma (7)

Answer 28

1. loss of **p16** and cyclin overexpression in earlier lesions 2. loss of **FHIT** (tumor suppressor gene) 3. **Bcl2** overexpression 4. abnormal expression / mutation of **p53 ** 5. **telomerase** dysregulation 6. **EGFR** overexpression (86%) 7. **cyclin D1 over expression** and 2q, 18q, HER-2 neu, bcl-2 gene alterations occur at the transition to invasive cancer

Question 29

this cancer may produce ADH or ACTH (cushing's: body exposed to increased cortisol levels)

Answer 29

small cell carcinoma -pt can have greatly increased free cortisol urine levels

Question 30

Molecular testing for these two markers is indispensible for lung adenocarcinomas

Answer 30

EGFR and ALK