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Flashcards in Molecular Pathology - Lung Deck (15)
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1

Recall the most common, usually mutually exclusive mutations found in lung adenocarcinoma, and their frequency.

Who do they usually affect?

K-RAS (25%) - Smokers

EGFR (15%, usually L858R) - Asians

ALK / RET / ROS (10%) - Younger patients

Minor: RET, BRAF, ERBB2, MET

2

What mutations are often found in squamous cell carcinoma of lung?

Smoking related mutations, usually p53. No driving mutations.

FGFR3 and PI3K/PTEN/AKT mutations are less common.

3

With respect to lung adenocarcinoma:

How common are p53 mutations?

What is the significance of STK11 mutations?

What is the significance of PI3K/PTEN/AKT mutations?

p53 mutations are found in 50% of lung adenocarcinomas

STK11 mutations are found in association with K-RAS and confer resistance to MEK inhibitors.

PI3K/PTEN/AKT confer resistance to EGFR inhibitors.

4

What mutations are usually found in small cell lung carcinoma?

TP53, RB1.

MYC-amplification less often.

5

What morphologies are associated with EGFR mutation in lung adenocarcinoma?

Bonus: Recall their significance.

Acinar - More likely to recur in presence of cribriforming

Lepidic - Usually adenocarcinomas in situ

Micropapillary - Increased lymph node metastasis

Papillary

6

What morphologies are seen in lung adenocarcinoma with:

K-RAS mutation?

ALK/ROS/RET?

K-RAS: Solid-predominant

ALK/ROS/RET - Extracellular mucin and prominent signet ring cells

7

Describe the mutations found in lung adenocarcinoma in situ.

Follows lung adenocarcinoma, with particular association with EGFR mutations. 

8

What mutations are found in invasive mucinous adenocarcinomas?

Usually K-RAS mutations. 

9

What is the significance of MET mutations?

Found in at least lung adenocarcinomas, they confer aggressive behavior, but can be targeted by MET inhibitors like crizotinib

10

What mutations are found in large cell carcinomas?

TP53, K-RAS

11

What mutations are found in adenosquamous carcinomas?

Same as adenocarcinomas; EGFR, K-RAS, ALK-RET-ROS

12

What mutations are found in pleomorphic/sarcomatoid carcinomas?

MET and K-RAS.

EGFR in asian populations.

13

What is NUT carcinoma?

How it is characterized?

A rare and aggressive carcinoma that affects the head & neck, lung, and salivary glands.

Sheets of undifferentiated cells with NUT overexpression and NUTM1 gene fusion.

14

What salivary gland tumors are found in lung, and what mutations drive them?

Mucoepidermoid carcinoma - MAML2 rearrangement

Adenoid cystic carcinoma - MYB rearrangement

Hyalinizing clear cell carcinoma - EWSR1 rearrangement

15

What are the preferred methods of detection for:

EGFR?

K-RAS

ALK?

 

EGFR - Sequencing

K-RAS - Sequencing

ALK - FISH