Lung Cancer

Question 1

What does TTF1 stain for?

Answer 1

Lung cancer / thryoid malignancies

Question 2

What does P63 stain?

Answer 2

Squamous differentiation

Question 3

What does ALKD5F3 stain?

Answer 3

Specific genetic rearrangement

Question 4

If test positive for ALKDF3 what you do?

Answer 4

FISH

Question 5

What is ALK-rearranged lung adenocarcinoma

Answer 5

Stage 4 disease

Question 6

What do you treat ALK rearranged lung adenocarcinoma with?

Answer 6

Crizotinib

Initial dramatic response

Question 7

How is lung cancer diagnosed?

Answer 7

Sputum sample

Bronchial washings and brushings

Bronchoalevolar lavage

Transbronchial FNA (EBUS)

Percutaneous transthoracic FNA

Question 8

What is the sputum technique?

Answer 8

Early sample

Pick and smear - fixation 95% alc

Question 9

Whati s bronchial washing?

Answer 9

1st to 3rd bronchial lesions

During bronchoscopy

Wash saline over bronci

Reaspirate

Taken back to lab

Prepared by cytocentrifuge or liquid based method

Question 10

What is bronchial brushing?

Answer 10

Direct sample of mucosal

Brush scraped over lesion

Get cells out of brush

Question 11

What is bronchoalveolar lavage?

Answer 11

Goes deeper

5th - 6th bronchi

Distal lung irrigated with 20- 50ml aliquots of saline

re-aspiration

Question 12

What is transbronchial DNA (EBUSCOPE)

Answer 12

Standard practice

Ultrasound guided

Fiberoptic
Direct visualisation

Sample nodes or disease just outside airways

Question 13

What is FNA?

Answer 13

Fine needle aspiration

Question 14

Whati s percutaneous transthoracic FNA CT guided?

Answer 14

Peripheral lung lesion

Go from outside body

Higher risk

Question 15

How does FNA squash smear prep work?

Answer 15

Take that piece of tissue
Squish between two slides
WTF

Question 16

What is cell block preparation?

Answer 16

Material washed in saline
Centrifuged
Plasma added
Thrombin added
Fish out clot
Fixed in formalin

Question 17

What are reporting categories for cytology?

Answer 17

Benign/neg
Atypical
Suspicious malig
Malig
Non-diagnostic/unsatisfactory

Question 18

What are the major categories of lung cancers?

Answer 18

Adenocarcinoma (38%)

Squamous cell carcinoma (20%)

Small cell carcinoma (14%)

Large cell carcinoma

Adenosquamous carcinoma

Sarcomatoid carcinoma

Question 19

What is adenocarcinoma?

Answer 19

Invasive malignant epithelial tumour with glandular differentiation or mucin production

M=F

Most smokers

Increasing incidence compared to SqCCa

more peripheral than central

Extrathoracic metastases
-adrenal, bone, brain

Cohesive group of malignant cells

Question 20

What is adenocarcinoma in situ?

Answer 20

Neoplastic glandular proliferation 3cm or less that has a pure lepidic growth along alveolar walls

Precurser lesion, metastatic potential

If resected, curable

No stromal, vascular or pleuran invasion

Rarely mucinous

Question 21

What does lepidic mean?

Answer 21

Implies cells are resting on top of aleolar walls, but not invading tissue

Question 22

What doe adenocarcinoma in situ look like?

Answer 22

Glass nodule/opacity

Question 23

What is squamous cell carcinoma?

Answer 23

Malignant epithelial tumour showing keratinisation and / or intercellular bridges

Smoking pattern

More M > F

Central > peripheral

Precurser lesion of squamous dysplasia / carcinoma in-situ

Prone to necrosis and cavitation

Locally aggressive. less frequent metastasis

Question 24

What is small cell carcinoma?

Answer 24

Highly aggressive malignant epithelial tumour, v. strongly associated with smoking

Central&raquo_space;»> peripheral

Extopic hormone production common
- cushing etc

Highly aggressive, widespread metastases and virtually always fatal

Treated with chemoradiation

Question 25

What does SCC look like in histology?

Answer 25

Scant cytoplasm
Finely granular chromatin
Absent/inconspicuous nucleoli
Nuclear molding, necrosis
Mitoses++
Immunohistochemistry:
  - CD5/6
  - Synaptophysin
  - Chromogranin 
  - TTF1

Electron microscopy:
- Neuroendocrine granules in 2/3

Question 26

What ancillary studies are available on neoplastic cytology specimens?

Answer 26

Cytochemical stains
Immunocytochemical stains
Flow cytometry
Electron microscopy
PCR based techniques
FISH

Question 27

Why do you subtype NSCLC?

Answer 27

Non small cell lung cancer means adeno or squamous

Approx 70% of patients have unresectable disease
Cytology sample is all you get

Want to define adeno or squamous now though

Question 28

How do you subtype NSCLC?

Answer 28

Morphology and Immunohistochemistry

PAD+d (mucin)
TTF1 - confirm lung + adeno
p63 - squamous
CK5/6 - squamous

New markers Napsin A
P40

Question 29

What is mucin?

Answer 29

Protein commonly upregulated in adenocarcinomas

Question 30

Why subtype?

Answer 30

Clinicians and drugs/treatments

Give appropriate treatment

Dont give bevacizumab to squamous :/

Question 31

What are the two main mutations and treatments in adenocarcinoma?

Answer 31

EGFR mutation - treated with –EGFR inhibitors

ALK-rearranged adenocarcinoma
-Crizotinib

Pemetrexed

Question 32

Where are the mutations in EGFR-mutated lung adenocarcinoma?

Answer 32

exon 19 and 21

Question 33

What race is most likely to exhibit EGFR mutations?

Answer 33

east asian 30-50%
Non smokers

Lepidic growth

PCR-based detection

Predicts response to EGFR TKIs

Erlotinib gefitinib

Eventual resistance

Question 34

Where do you find ALK-rearranged lung adenocarcinomas?

Answer 34

First described in 2007

Uncommon ~4% of NSCLC

Younger people

Adenocarcinoma with solid signet ring or mucinous cribiform pattern

Detection via IHC, FISH and RT-PCR
- Fish = gold standard
Vysis ALK fish break apart fish probe

Question 35

What drug do you use to treat ALK lung cancer?

Answer 35

Crizotinib