B42. Malignant lung tumors

Question 1

By location: what types of lung cancer typically appear:

1) Centrally, often near a main bronchus
2) Peripherally
3) Peribronchial
4) Apically

Answer 1

1) Squamous cell carcinomas
2) Adenocarcinomas and Large-Cell carcinomas (undifferentiated type)
3) Small cell carcinomas
4) Pancoast tumors - non-small cell types (typically adenocarcinoma or large cell carcinoma)

Question 2

Where do lung cancers typically metastasize to?

Answer 2

• Brain
• Bones
• Liver
• Adrenal glands
• Skin and serous membranes

Question 3

Frequencies of the various types of lung cancer, in order

Answer 3

1. Adenocarcinoma 40%
2. Squamous cell carcinoma 30%
3. Large cell carcinoma 15%
4. Small cell carcinoma 15%
5. Mixed/Combined types
6. Carcinoid tumors

Question 4

Small cell lung cancer

Risk factors

Cell of origin

Answer 4

It is caused by smoking

Kulchitsky cells, aka neuroendocrine cells, aka enterochromaffin cells of the lung

potentiall from Clara cells stem cells of the lung.

Question 5

Where does lung cancer rank in terms of frequency and mortality in cancers of men and women

Answer 5

It is 2nd most frequent in both sexes, behind prostate and breast cancers

1st most frequent cause of cancer-related death in both sexes.

Question 6

What lung cancers are caused by smoking?

What cancers are most frequent in non-smokers?

Answer 6

Smoking

• squamous cell carcinoma in males
• adenocarcinoma in females
• small cell carcinoma.
• Large cell carcinoma

Non-smokers

• adenocarcinoma
• bronchioalveolar carcinoma
• carcinoid tumors

Question 7

What are the early mutations in most lung cancers?

What are the main mutations associated with small and non-small cell lung cancers?

Answer 7

• 3p deletions occur early.
• Inactivation of tumor suppressor genes on chromosome 3 short arm.
• present in >80% of both SCLCs and NSCLC
• p53 deletions occur late, shortly before overt cancer

Small cell lung carcinoma:

• RB mutations in ~90%
• p53 mutations in ~90%

Non-small cell

• KRAS activating mutations in adenocarcinomas
• EGFR activating mutations in adenocarcinomas - non-smoking asian females.
• p53 in >50%
• p16 in >50% (is a CDK inhibitor)

Question 8

What are the main carcinogens in cigarette smoke?

What are the other major carcinogens that cause lung cancer besides smoking?

Answer 8

PAH in smoke, but there are dozens of chemical carcinogens in it.

Radon - 2nd most frequent cause of lung carcinoma in the US. forms from the decay of uranium found in soil. Accumulates in closed spaces, basements.

Asbestos - lung carcinoma and mesothelioma. Combined smoking plus asbestos exposure skyrockets cancer risk. 55 times higher than nonsmokers with no asbestos exposure.

Marijuana

Work place exposure: uranium, coal products, arsenic, gas exhaust.

Question 9

What is Horner Syndrome?

Answer 9

M E A PT

• Miosis - small constricted pupil
• Enopthalmos - sunken in eyes (like in hypothyroidism)
• Anhydrosis - no sweating
• Ptosis - droopy eyelids

Results from compression of sympathetic chain, and suppressed activity of the cervical sympathetic ganglia, usually by a pancoast tumor.

Question 10

What is the main mutation in small cell lung carcinoma

Question 11

How does Rb protein inhibit mitosis?

How does p16 inhibit mitosis?

Answer 11

RB binds to and inhibits the action of E2F family transcription factors, essential for mitosis.

p16 inhibits Cyclin D1, one of whose targets is RB. Cyclin D1 phosphorylates and inactivates Rb, and p16 is a CDK inhibitor.

Question 12

What are the hormones that can be produced by Small Cell Lung Cancers?

Answer 12

ACTH

ADH

Gastrin Releasing peptide

Calcitonin.

Question 13

What type on non-small cell lung cancer causes paraneoplastic syndrome? What hormone does it release?

Answer 13

Squamous cell carcinoma

PTH-rp

Question 14

What paraneoplastic syndromes are caused by lung tumors?

Answer 14

• Hyper parathyroidism from PTH-rh
• Cushing syndrome from ACTH
• SAIDH from ADH
• Neuromuscular syndromes such as myasthenia gravis, polymyositis
• Finger clubbing, hypertrophic pulmonary osteoarthropathy
• Hematologic disorders, hypercoagulability. especially from adenocarcinomas.
  
  • DIC
  • Migratory thrombophlebitis - Trousseau’s sign of malignancy. Venous thromboses of superficial veins, causing inflammation behind it.

Question 15

Describe carcinoid tumors

Answer 15

Typical carcinoids: slow growing, benign with very rare metastases, low pleomorphism. Can progress to atypical carcinoid.

Atypical carcinoids: higher mitoses, more variability, areas of focal necrosis. Can metastasize. Can transform into small cell carcinoma.

Has a much better prognosis than other lung cancers: 5yrS is >85%, and 55% 10yrS.

both types arise from neuroendocrine cells in the bronchiolar mucosa.

luminal carcinoid tumors: spherical masses growing into the lumen.

mucosal plaques: grow through the bronchial wall into the peribronchial tissue.

In rare cases, cause carcinoid syndrome: attacks of diarrhea, flushing, and cyanosis.