Lung Cancer

Question 1

Hamartoma

Answer 1

“coin lesion” and consists of mature cartilage admixed with fat, fibrous tissue, and blood vessels

Question 2

Inactivation of what gene is a common early event? What gene inactivation are late events?

Answer 2

Inactivation of the tumor suppressor genes located on the short arm of chromosome 3 (3p) is a very common early event. Mutations of the TP53 tumor suppressor gene and the KRAS oncogene occur relatively late.

Loss of chromosomal material on 3p, are found even in benign bronchial epithelium of smokers without lung cancer.

Question 3

Adenocarcinomas in non-smoking women contain mutations that activate what?

Answer 3

Activate the EGFR receptor. EGFR stimulates downstream pro-growth pathways involving RAS, PI3K, and other signaling molecules.

Commonly seen in non-smoking Asian women.

Question 4

How are chemicals converted into carcinogens?

Answer 4

Chemicals require metabolic activation via the P-450 monooxygenase enzyme for conversion into carcinogens. Individuals with P-450 polymorphisms have an increased capacity to activate procarcinogens.

Question 5

What are BASCs?

Answer 5

Bronchioalveolar stem cells (BASCs) facilitate epithelial regeneration. After lung injury, multipotent BASCs proliferate and replenish the normal cell types (bronchiolar Clara cells and alveolar cells).

Postulated that BASCs incur the initiating hit that enables these cells to escape normal “checkpoints”

Question 6

Pattern of epithelial changes:

Answer 6

Basal cell hyperplasia and squamous metaplasia –> squamous dysplasia and carcinoma in situ –> invasive cancer

Question 7

What is the precursor to adenocarcinoma?

Answer 7

AAH (atypical adenomatous hyperplasia) = epithelial proliferation composed of cuboidal to low-columnar cells that demonstrate nuclear hyperchromasia, pleomorphism, and prominent nucleoli.

Question 8

Progression to adenocarcinoma:

Answer 8

AAH –> adenocarcinoma in situ –> minimally invasive adenocarcinoma (<3 cm in diameter with an invasive component of <5 mm) –> invasive adenocarcinoma (a tumor of any size with an area of invasion >5 mm)

Question 9

What serves as a scaffold for adenocarcinoma in situ growth?

Answer 9

Alveolar septa

Question 10

Where does squamous cell carcinoma arise? Where does it spread?

Answer 10

Arise centrally in major bronchi and eventually spread to local hilar nodes.

Question 11

What proceeds squamous cell carcinoma?

Answer 11

Squamous metaplasia or dysplasia in the bronchial epithelium, which then transforms to carcinoma in situ, a phase that may last for several years.

Question 12

What are the two neuroendocrine cell lung cancers? What do they stain positive for?

Answer 12

Small cell (poor differentiated)

Carcinoid (well differentiated)

Stain positive for chromogranin.

Question 13

“Crush artifact”

Answer 13

Small cell carcinoma

Question 14

Nuclear molding

Answer 14

SCC: resulting from close apposition of tumor cells that have scant cytoplasm

Question 15

Typical patterns of syndromes for cancer types:

Answer 15

Squamous cell neoplasms = Hypercalcemia

Adenocarcinomas = Hematologic syndromes

Small cell carcinomas = Neurologic syndromes

Question 16

Bronchial carcinoids normally occur in what population? Where do most of them occur?

Answer 16

Young adults. They occur in the main bronchi.

Question 17

SCC stains positive for what?

Answer 17

Chromogranin A
Neuron-specific Enolase
Synaptophysin

Bronchial carcinoid cancers also stain positive for these.

Question 18

Hypertrophic osteoarthropathy is associated with which type of lung cancer?

Answer 18

Adenocarcinoma. Digital clubbing and sudden-onset symmetrical arthropathy, usually involving the wrist and hands.

Question 19

Adenocarcinomas stain positive for mucin. In order to demonstrate intracellular mucin what stains must be used?

Answer 19

PAS or Mucicarmine

Question 20

Lambert-Eaton Syndrome is most associated with?

Answer 20

Small cell lung cancer

Question 21

What type of cancer can secrete beta-HCG?

Answer 21

Large cell carcinoma. Can lead to very high levels of estrogen and painful gynecomastia (breast enlargement) in males as paraneoplastic signs

Question 22

What genetics are associated with adenocarcinoma?

Answer 22

EGFR, ALK, KRAS mutations

EGFR & ALK = receptor tyrosine kinases
KRAS = GTPase

Question 23

What is associated with migratory thrombophlebitis, Trousseau’s sign, and murantic endocarditis, and DIC?

Answer 23

Adenocarcinoma.

Question 24

What is associated with hypertrophic pulmonary osteoarthropathy?

Answer 24

Adenocarcinoma and other NSCLC.

Medical condition combining clubbing and periostitis of the small hand joints, especially the distal interphalangeal joints and the metacarpophalangeal joints. Distal expansion of the long bones as well as painful, swollen joints and synovial villous proliferation are often seen.

Clubbing and increased bone deposition on long bones. Do a bone scan and radiograph.

Question 25

Adenocarcinomas will have either of what three structures?

Answer 25

Mucin, Glands, or Papillary structures.

Question 26

Large Cell Carcinoma: Large _____ undifferentiated carcinoma cells with _______ _________.

Answer 26

Large undifferentiated carcinoma cells with prominent nucleoli. Also have abundant cytoplasm.

Question 27

Mutations associated with SCC?

Answer 27

TP53, RB, MYC, 3p deletion.

Question 28

Which lung cancer has cells without nucleoli?

Answer 28

SCC. They also have scant cytoplasm.

Question 29

SVC vs. Pancoast Tumor

Answer 29

SVC = usually SCLC

Pancoast = usually NSCLC

Question 30

Most carcinogenic asbestos fiber and less carcinogenic fiber?

Answer 30

Crocidolite (amphibole) most carcinogenic.

Chrysotile (serpentile) less carcinogenic.

Question 31

Inactivation of what tumor suppressor genes are associated with mesothelioma?

Answer 31

BAP1 and CDKN2/INK4a.

Question 32

What two lung carcinomas have microvilli?

Answer 32

Mesothelioma = long microvilli

Adenocarcinoma = short microvilli