11.30: Pulm IV

Question 1

What is a hamartoma?

Answer 1

Most common benign tumor of the lung

Question 2

What is the Most common benign tumor of the lung?

Answer 2

Hamartoma

Question 3

What is most common primary malignant tumor of lungs?

Answer 3

95% are carcinomas

- Carcinoma is an epithelial, malignant tumor

Question 4

Prevalence of lung cancers?

Answer 4

• 2nd most common tumor in men and women
• # 1 in men is prostate
• # 1 women breast
• ***However, lung cancer is most common cause of death in both men and women

Question 5

Most common etiology of lung cancer?

Answer 5

• Smoking
• Average smoker 10 x greater risk
• Heavy smoker 60 x greater risk

Question 6

What do most smoking related cancers have in common?

Answer 6

P53 abnormalities

Question 7

Factors outside of tobacco increasing risk of lung cancer?

Answer 7

1. High dose ionizing radiation
2. Asbestos
3. Radon from air pollution
4. Genetic Predisposition

Question 8

What is 2 compartment model of lung cancer pathogenesis?

Answer 8

• Smokers are more likely to damage upper airways and are more likely to get SQC or SCLC
• Non smokers more likely to get ADC in terminal respiratory unit

Question 9

What is SQC?

Answer 9

“Squamous cell carcinoma”

Question 10

What is SCLC?

Answer 10

Small cell carcinoma

Question 11

Which cancers are smokers most likely to get?

Answer 11

1. SCLC

2. SQC

Question 12

Which type of lung cancer are non smokers more likely to get?

Answer 12

ADC: “Adenocarcinoma”

Question 13

Key mutations leading to ADC?

Answer 13

1. EGFR

2. Kras

Question 14

In which organ is direct association between smoking and carcinoma not shown?

Answer 14

• Breast

- Correlative evidence in most others

Question 15

Break down of lung carcinoma types?

Answer 15

1. Small cell carcinoma (SCC) 20%
2. Non SCC 80%
   a. Adenocarcinoma: “ADC” 40%
   b. Squamous cell: “SQC” 30%
   c. Large cell/other: 10%

Question 16

Which type of lung cancer more responsive to surgical therapy?

Answer 16

• Non small cell carcinomas

* **SCCs are not responsive to surgery as it is systemic in metastasis by time it is discovered

Question 17

Treatment of two main types of lung cancer?

Answer 17

SCC: radiation as likely inoperable and systemic
NSCC: Surgery

Question 18

What is the function of PTH?

Answer 18

• Elevate serum Ca

- SQC can be associated with inappropriate PTH secretion

Question 19

Who is at high risk for SQC?

Answer 19

1. Men

2. Smokers

Question 20

How is SQC characterized in morphology?

Answer 20

Any of the following:

1. Intercellular bridges
2. Keratinization
3. Diffuse P63/40 immunoreactivity

Question 21

Where is SQC usually located?

Answer 21

• Large, Centrally based mass in thorax
• 70 - 90 % lymph node involvement
• 7% spread outside thorax

Question 22

What happens in SQC grows too large?

Answer 22

• Outstips vascular supply to become necrotic w/ cavitating center

Question 23

What is metaplasia?

Answer 23

Movement from one epithelium type to another

Question 24

Progression of precursor lesions for SQC?

Answer 24

1. Squamous metaplasia
2. Mild Dysplasia, moderate, severe
3. Carcinoma in situ: full thickness with all layers involved and basement membrane intact
4. Invasion characterized by intercellular bridges and keratinization

Question 25

What is Invasion characterized by intercellular bridges and keratinization characteristic of?

Answer 25

SQC

Question 26

Most common genetic abnormality with SQC?

Answer 26

1. p53 mutation

Question 27

Which tumor has highest frequency of P53 mutation?

Answer 27

SQC

Question 28

Who is ADC seen in?

Answer 28

- Women > men - More often in non smokers - More often located in periphery

Question 29

Progression of precursor lesions in ADC?

Answer 29

1. AAH "Atypical adenomatous Hyperplasia" 2. AIS "Adenocarcinoma in situ" 3. MIA "Minimally invasive Adenocarcinoma"

Question 30

What must tumor have to be ADC?

Answer 30

EITHER..... 1. Gland forming 2. Contain intracellular mucin 3. TTF1 positive

Question 31

What is irregular spiculated mass indicative of?

Answer 31

ADC

Question 32

What is AAH?

Answer 32

"Atypical adenomatous Hyperplasia" - Less than 5mm - Well demarcated - Lined by cuboidal to low columnar epithelium - Mild atypia * **Incidental finding, not pathological

Question 33

What is AIS?

Answer 33

"Adenocarcinoma in situ" - 3cm or less - Growth along pre existing structures but do not invade - Alveolar architecture is preserved

Question 34

What is MIA?

Answer 34

"Minimally invasive Adenocarcinoma" - 3 cm or less - INVASIVE focus > 5mm - NO invasion into pleura, lymphatics or vessels

Question 35

Main driver mutation in ADC?

Answer 35

1. EGFR mutation - Females, asians, on smokers - Tyrosine kinase receptor becomes always active triggering proliferation - Can be inhibited 2. kRAS - Confer resistance to EGFR therapy - No targeted therapy: poor outcome 3. ALK

Question 36

Characteristics of large cell carcinoma?

Answer 36

1. Undifferentiated 2. Poor prognosis: 5 year survival 2-3% 3. Metastasize early to liver, adrenal, brain

Question 37

Oat is oat cell carcinoma?

Answer 37

Another name for SCC

Question 38

Another name for SCC?

Answer 38

Oat cell carcinoma

Question 39

Characteristics of SCC?

Answer 39

- Rapidly growing, high grade, neuroendocrine tumor - Strongly associated with smoking - High, fast metastasis - Leads to paraneoplastic syndromes - Rarely resectable: radio/chemotherapy - 2 year survival of 5-8%

Question 40

Histologic characteristics of SCC?

Answer 40

```  Densely packed “small blue” tumor  size 3 x of small, resting lymphocyte  Round to ovoid nucleus  Scant cytoplasm  Finely dispersed chromatin  High mitotic activity  Necrosis present ```

Question 41

Genetic components of SCC?

Answer 41

- 100% show inactivation of P53 and RB

Question 42

What is bronchial carcinoid?

Answer 42

- Low grade malignant neuroendocrine tumor - Rarely metastatic - Good surgical prognosis

Question 43

Most common clinical features of lung cancer?

Answer 43

1. Cough 2. Weight Loss 3. Chest pain 4. Dyspnea

Question 44

Downstream features of lung cancer?

Answer 44

 Pneumonia, abscess –tumor obstruction of airway  Pleural effusion-tumor spread into the pleura  Pericardial tamponade- pericardial involvement  Hoarseness- recurrent laryngeal nerve invasion  Dysphagia- esophageal invasion  Diaphragm paralysis-phrenic nerve involvement  Rib destruction-chest wall invasion

Question 45

How does lung cancer cause hoarseness?

Answer 45

Impingement upon recurrent laryngeal nerve

Question 46

What is superior vena cava syndrome?

Answer 46

Obstruction of SVC resulting in facial swelling, cyanosis, and dilation of head and neck veins

Question 47

What is pancoast tumor?

Answer 47

- Apically located tumor that can dester 1st/2nd rib | - May show horner syndrome

Question 48

What is horner's syndrome?

Answer 48

* ***Due to sympathetic plexus involvement 1. Ptosis 2. Miosis 3. Anhydrosis

Question 49

What are paraneoplastic syndromes?

Answer 49

- Cancer symptoms that cannot be explained by spread of cancer or its elaboration of hormones * *EG: Tumor not in adrenal area producing adrenal hormones

Question 50

What is cushing's?

Answer 50

Paraneoplastic syndrome with excess ADH expression

Question 51

What is hydrothorax?

Answer 51

Fluid in pleural space from CHF

Question 52

What is chylothorax?

Answer 52

Lymphatic fluid in pleural space

Question 53

Most common malignant pleural tumor?

Answer 53

- Mesothelioma - Related to asbestos - 25 - 50 year latent period - Rarely survive > 1 year

Question 54

Genetic component of mesothelioma?

Answer 54

1. P16 deletion | 2. NF2 deletion

Question 55

Clinical presentation of mesothelioma?

Answer 55

1. Chest pain 2. Dyspnea 3. Recurrent pleural effusion

Question 56

Most common malignant tumor of lung?

Answer 56

Metastasis from other area