Lung Tumors

Question 1

What are different types of lung tumors?

Answer 1

• Brochogenic Carcinoma – 90 – 95%
  
  • Originate in the bronchial (or bronchiolar ) epithelium
• Carcinoids – 5%
• Other tumors – 2- 5%

Question 2

Describe the incidence of bronchogenic carcinomas:

Answer 2

• Public enemy # 1 in industrialized countries
• Incidence is decreasing in men and increasing in women
  
  • Most frequent fatal malignancy in men and women
• Most common visceral malignancy in males
  
  • 1/3 of cancer deaths in males/ 7% of cancer deaths in both sexes
  • Males > Females
• Dramatic increase in incidence in women (cigarette smoking)
  
  • Lung Ca has surpassed breast Ca as a cause of cancer death in women
• A disease of middle and late adult life, with a peak incidence in 50s or 60s
  
  • < 2% below age 40

Question 3

What are the etiologies of bronchogenic carcinomas?

Answer 3

• Tobacco smoking
• Industrial hazards
• Air pollution
• Molecular genetics
• Scarring

Question 4

What is the statistical evidence for tobacco smoking as a cause of bronchogenic carcinoma?

Answer 4

• Association between frequency of lung ca. & amount of daily smoking
  
  • Smokers 10-fold greater risk
  • Heavy smokers 20-fold greater risk
  • X smoking for 10 yrs, reduces risk to control level
• Tendency to inhale
• Duration of smoking habit
  
  • Pack year - calculated by multiplying the number of packs of cigarettes smoked per day by the number of years the person has smoked
• Other associations – lip, tongue, mouth, pharynx, larynx, esophagus, UB, pancreas, kidney

Question 5

What is the clinical evidence for tobacco smoking as a cause of bronchogenic carcinoma?

Answer 5

• Histologic changes in the respiratory tract of smokers
  
  • 96.7% smokers - atypical changes in bronchial epithelium
  • 0.9% control subjects - similar changes

Question 6

What is the experimental evidence for tobacco smoking as a cause of bronchogenic carcinoma?

Answer 6

• Cancer induction in experimental animals by exposure to tobacco smoke
• Potential carcinogens –
  
  • Initiators (benzopyrene)
  • Promoters (phenol derivatives)
• Radioactive elements (carbon-14, potassium-40)
• Contaminants (arsenic, nickel, molds, additives)
• Experimental mice – Skin tumors, few lung cancers (bronchioloalveolar carcinoma)

Question 7

What industrial hazards potentially lead to bronchogenic carcinoma?

Answer 7

• Radiation – Increased incidence in Hiroshima/Nagasaki survivors
• Uranium miners – lung cancer rates higher than general population
• Asbestos – Much higher risk than general population of developing lung cancer
• Other hazards – Nickel, chromates, coal, mustard gas, arsenic, beryllium, iron

Question 8

Why are people exposed to asbestos at a higher risk of developin bronchogenic carcinoma?

Answer 8

• Asbestos w/o smoking ⇒ 5 times greater risk than gen. pop.
• Asbestos + smoking ⇒ 50 – 90 times greater risk than gen. pop.
• Latent period ⇒ 10 – 30 years
• 1/5 deaths – Lung Ca.
• 1/10 deaths – Mesothelioma
• 1/10 deaths – GI Ca

Question 9

• How can air pollution increase the risk of bronchogenic carcinoma?
• Who is partciularly at risk?

Answer 9

• Indoor air pollution – Radon exposure
  
  • ubiquitous radioactive gas
  • lung cancer in non-smokers may be attributed to radon exposure
• Miners exposed to higher concentrations

Question 10

What are the genes/proteins potentially involved in bronchogenic carcinoma?

Answer 10

• Genetic alterations which accumulate and ultimately lead to neoplasia
• Oncogenes
  
  • C-myc ⇒ small cell carcinoma
  • K-ras, EGFR, EML4-ALK ⇒ adenocarcinoma
• Tumor suppressor genes
  
  • p53
  • Retinoblastoma
  • ? Genes on short arm of Chromosome 3

Question 11

__________ causes DNA damage at the same codons of the p53 gene

Answer 11

Benzopyrene causes DNA damage at the same codons of the p53 gene

• Familial clustering and variable risk among heavy smokers suggest genetic predisposition

Question 12

• What is the role of scarring in brochogenic carcinoma?
• Which type is scarring usually seen?

Answer 12

• “Scar cancers” – Cancers occurring in the vicinity of pulmonary scars
  
  • Usually adenocarcinomas
• In most cases, the scar is a response to the tumor
  
  • Sometimes, scar precedes cancer (old infarcts, wounds, granulomatous infections)

Question 13

**Bronchogenic Carcinoma: **

Clinical Features and Course

Answer 13

• Usually present in their 50s
• Average duration of symptoms ⇒ 7 months
• Major presenting complaints:
  
  • cough (75%)
  • wt loss (40%)
  • chest pain (40%)
  • dyspnea (20%)
• Increased sputum production – Cytology
• May be diagnosed upon secondary spread

Question 14

What is a Pancoast tumor? What can it lead to?

Answer 14

• Tumor at the extreme apex of the lung
• Involvement of superior cervical sympathetic ganglion
  
  • Horner’s syndrome:
    
    • Ipsilateral lid lag
    • Miosis
    • Ipsilateral anhydrosis

Question 15

What are the two major classifications of bronchogenic carcinomas?

Answer 15

1. Small cell carcinoma
2. Non-small cell carcinoma

Question 16

What are the different types of small cell carcinoma?

Answer 16

• Oat cell (lymphocyte-like)
• Intermediate cell (polygonal)
• Combined (usually with squamous)

Question 17

What are the different types of non-small cell carcinoma?

Answer 17

• Squamous cell (epidermoid) carcinoma
• Adenocarcinoma
  
  • Glandular (acinar) with mucin
  • Papillary
  • Solid
  • (Lepidic) Bronchioloalveolar
• Large cell carcinoma
  
  • Neuroendocrine
  • Undifferentiated
  • Giant cell
  • Clear cell
• Adenosquamous carcinoma

Question 18

Small cell vs. non-small cell carcinomas based on reponse to treatment:

Answer 18

• Small cell carcinoma
  
  • responds well to chemotherapy
  • does not respond to surgery
• ​Non-small cell carcinoma
  
  • responds well to surgery depending on stage of the tumor
  • chemotherapy is less effective

Question 19

What are the pharmacologic options for treating adenocarcinoma and ** squamous cell carcinoma**?

Answer 19

1. Epidermal growth factor receptor (EGFR), KRAS and EML4-ALK mutations
   
   • Confined to adenocarcinoma
   • Predictive of response (EGFR) and resistance (KRAS) to:
     
     • EGFR TKIs – Erlotinib (Tarseeva) and Gefitinib (Iressa)
   • ALK inhibitor - Crizotinib
2. Bevacuzimab – Antibody to vascular endothelial growth factor (VEGF)
   
   • Toxicity in SqCC (hemorrhage)
3. Pemetrexed
   
   • Activity in non-SqCC

Question 20

Squamous cell carcinoma:

• Incidence:
• Clinical presentation:
• Histology:

Answer 20

• The most common type in Males
• Cigarette smoker
• Central cavitary necrosis
  
  • Usually arise centrally (main or lobar bronchi)
  • Usually endobronchial, polypoid growth
• Histology:
  
  • keratin formation, intercellular bridges, atypia and invasion
  • Well/moderately/poorly differentiated subtypes depending on degree of squamous differentiation

Question 21

Adenocarcinoma:

• Incidence:
• Clinical presentation:

Answer 21

• Most common type in women and non-smokers (most patients with adenocarcinoma are smokers)
• Most common form of lung carcinoma in USA
• Usually peripheral with pleural retraction or puckering
  
  • Associated with scarring
• Grow more slowly, metastasize more frequently than squamous cell carcinoma
• Asymptomatic (peripheral tumor) – Late diagnosis

Question 22

Bronchioloalveolar carcinoma:

• Incidence:
• Clinical presentation:
  
  • What has a worse prognosis?
• Histology:

Answer 22

• A subset of adenocarcinoma
• 1% – 9% of all lung carcinomas
• Gross
  
  • Single peripheral nodule
  • Multiple nodules (several lobes/bilateral) –
    
    • multifocal/aerogenous spread
  • Diffuse pneumonia-like infiltrate
• Histology — Lepidic spread (tumor cells spread along alveolar septa)
  
  • Nonmucinous (Clara cells, type 2 pneumocytes) – 2/3 cases
  • Mucinous (tall columnar mucinous cells) – Worse prognosis

Question 23

Small cell carcinoma

• Incidence:
• Clinical presentation:
• Prognosis:

Answer 23

• 20 – 25% of lung cancers
• Predominantly in males, smokers, central location
• Highly malignant, median survival – 4 months
• Submucosal/circumferential infiltration
• Rare endobronchial polypoid growth
• Subclassification:
  
  • Oat cell
  • Intermediate cell
  • Mixed (small cell/large cell)
  • Combined (small cell/adeno or squamous)

Question 24

What is the clinical course of small cell carcinoma?

Answer 24

• Extensive necrosis, crush artifact
• Secretory granules of neuroendocrine type
• Metastasis by the time of diagnosis
  
  • 70% patients seen at advanced stage
• Ectopic hormone production (paraneoplastic syndrome)
• Excellent response to chemotherapy

Question 25

**Large cell carcinoma** * Incidence: * Clinical presentation: * Prognosis:

Answer 25

* 10 – 15% of lung cancers * **Pleomorphic, large cells without differentiation** * Ultrastructural evidence of glandular or squamous differentiation * 5-year survival 6% * **Giant cell carcinoma** * Highly malignant * Mostly peripheral * \< 10 month survival

Question 26

**Adenosquamous carcinoma** * Incidence: * Clinical presentation:

Answer 26

* 1 – 3% of lung carcinomas * Definite evidence of **squamous cell carcinoma** and **adenocarcinoma** in the same neoplasm * **Peripheral tumor, associated with scar** * Clinical presentation and behavior **similar to adenocarcinoma** * **The majority of patients are smokers**

Question 27

Where do bronchogenic carcinomas metastasize?

Answer 27

* Metastases 1. **Hilar lymph nodes** 2. **Adrenal gland** (50%) 3. Liver (30%) 4. Brain (20%) 5. Bone

Question 28

What the **two most important factors** in determining survival and choice of therapy for bronchogenic carcinomas?

Answer 28

**Histologic type** and **tumor staging** are the two most important factors in determining survival and choice of therapy

Question 29

**Bronchogenic carcinoma** TNM classification

Answer 29

* Single most important prognostic parameter in non-small cell carcinoma * **Small cell carcinoma** * Limited disease: * hemithorax with/without LN involvement * Extensive disease: * Contralateral lung, distant metastasis

Question 30

Define **paraneoplastic syndrome:**

Answer 30

Symptom complexes that occur in patients with cancer that cannot be readily explained by local or distant spread; or by elaboration of hormones by tumor cells

Question 31

What are some examples of paraneoplastic syndromes caused by: 1. Small cell carcinoma 2. Squamous cell carcinoma

Answer 31

1. **Small cell carcinoma** * Cushing’s syndrome (ACTH) * Hyponatremia (inappropriate ADH secretion) * Carcinoid syndrome (serotonin) * Myasthenic syndrome (Eaton-Lambert syndrome) 2. **Squamous cell carcinoma**​ * **​​​​​​​​**Hypercalcemia (parathormone)

Question 32

What is the incidence of **carcinoid tumors**?

Answer 32

* 1-5% of all lung tumors * **Most patients are \<40 years of age** * **M=F** * _20-40% are non-smokers_ * **Low-grade** malignant neoplasms

Question 33

What can be seen **microscopically** in **carcinoid tumors**?

Answer 33

* Nests/ cords/ masses * Uniform cells with round nuclei * **“Salt & Pepper”** chromatin * **IHC:** NSE, chromogranin, synaptophysin +

Question 34

**Carcinoid Tumors** * Clinical Course: * Prognosis:

Answer 34

* **Hemoptysis, cough, obstructive symptoms** (due to intraluminal growth) – * infections, bronchiectasis, atelactasis or emphysema * **Carcinoid syndrome** – intermittent diarrhea, flushing and cyanosis. * Metastases occur rarely (1-5%) * **Usually follow a benign course for long periods and are amenable to resection** * 5 and 10 year survival (87%)